Lose Weight By Controlling The Fat Storage Hormone

Trouble Spot Nutrition

Created by Janet Hradil, Trouble Spot Nutrition is a 3 Phase Hormonal Solution That Melts Away Trouble Spot Fat In Less Than 15 Minutes A Day. Leptin, cortisol, and testosterone all have an influence on our weight issues, but not many of us know it. Janet Hradil has created Trouble Spot Nutrition with the intent of teaching people how their hormones affect their weight loss efforts, and how nutrition can easily correct hormone issues and help fight fat faster than ever before. In each of your fat cells, there is an enzyme, 11 beta-hydroxysteroid dehydrogenase-1 (Hsd), that takes inactive cortisone (a hormone) and turns it into cortisol, a fat storing compound. If you have high amounts of Hsd, you will have high amounts of fat storage. While Hsd is genetically determined, you can use nutrition to reduce levels and stop the unwanted fat storage, even on your trouble spots. Continue reading...

Trouble Spot Nutrition Summary


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Author: Janet Hradil
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Highly Recommended

I usually find books written on this category hard to understand and full of jargon. But the author was capable of presenting advanced techniques in an extremely easy to understand language.

My opinion on this e-book is, if you do not have this e-book in your collection, your collection is incomplete. I have no regrets for purchasing this.

Leptin And Central Nervous System

7.2.1 Circulating Leptin Gains Access to CNS Leptin is a 167-amino acid protein produced predominantly by adipocytes, although other organs and tissues including the placenta, stomach, and skeletal muscle also produce leptin.6,7 Circulating levels are generally low (5 to 10 ng ml) and are elevated in obese individuals in proportion to body fat, typically two- to four-fold.8,9 Indeed, the levels of circulating leptin exhibit a close relationship to body fat stores, although time of day, gender, age, sleep apnea, and acute variations in energy balance can all influence leptin levels.7,1012 Leptin appears to enter the central nervous system (CNS) via a saturable transport system. Thus, it is likely that this hormone gains access to hypothalamic receptors and regulates neural pathways that control appetite and energy expenditure through this saturable system and via circumventricular organs such as the median eminence.13,14 This saturable system appears to be one reason why obesity is...

Leptinresponsive Neural Pathways And Cardiovascular System

Although it has been nearly 10 years since the discovery of leptin, the mechanisms by which this hormone produces its biologic actions are only beginning to be understood. As described above, hypothalamic neurons that express either POMC CART or NPY AgRP are likely candidates to serve as the initial and primary mediators of leptin, including the sympathetic and cardiovascular responses to altered CNS leptin levels. Downstream mechanisms ultimately regulating pregan-glionic autonomic neurons controlling HR and vascular tone must be identified to gain a more complete understanding of the cardiovascular and sympathetic effects of leptin. One of the primary neurotransmitters in the POMC CART neuron is alpha melanocyte-stimulating hormone (aMSH). This peptide is cleaved from the POMC precursor and is a ligand for the melanocortin receptor (MC-R). The MC-R family consists of five known receptors. aMSH binds to the MC4-R within the hypothalamus and reduces food intake.6667 Several lines of...

Cardiovascular And Autonomic Effects Of Leptin

7.3.1 Leptin and Heart Rate Increasing attention is focused on the cardiovascular disease risk linked to the tachycardia commonly seen in obese patients.43031 Is increased circulating leptin a primary cause of the tachycardia associated with obesity Some human studies have observed correlations between circulating leptin levels and resting heart rate (HR), although the results are quite variable.32-34 In one study where HR was not correlated with leptin per se, spectral analysis suggested a relationship between elevated leptin and increased relative cardiac sympathetic tone.33 There have been several difficulties in delineating the effect of leptin on regulation of HR in animal studies. It is a common observation that anesthetized animals have reduced chronotropic responsiveness. Thus, it is not surprising that acute leptin administration to anesthetized animals generally has no effect on HR.35-37 Acute peripheral leptin administration to conscious rats has also been reported to have...

Cortisol Role and Circadian Rhythms in OSAS

Cortisol provides an important link between the immune system, sleep, and psychological stress. High levels of cortisol suppress the immune system, so excessively tired people are more susceptible to illness. Sleep disruption and sustained psychological stress increase cortisol concentration in the blood. Indeed, one night of lost sleep can raise cortisol concentrations by almost 50 by the following evening. High levels of cortisol suppress the immune system, so excessively tired people are more susceptible to illness (Foster and Wulff 2005). Indeed, one night of lost sleep can raise cortisol concentrations by almost 50 by the following evenings (Leprout, Copinschi, Buxton, and Van Cauter 1997). We studied circadian rhythms of cortisol in children with severe OSAS. Cortisol concentrations were determined every second hour between 8.00 p.m. and 8.00 a.m. during a 12 channels polisomnography. Cortisol among OSAS pediatric patients presented a significant growth in the interval included...


About half of all patients with major depression have a raised cortisol output, which tends to return to normal on recovery. It is most consistently associated with an 'endogenous' pattern of illness (Chapter 4.5.i3). While cortisol is always regarded as a 'stress' hormone, and is secreted in response to various types of acute stress, the stresses that commonly result in long-term hypercortisolaemia are poorly understood. The idea that there is a relatively specific link between chronic high cortisol levels and mood disorder is notably persistent. In major depression there is peripheral hypertrophy of the adrenal glands, measurable in MRI body scans, and an enhanced response to corticotropin. The MRI change, like the hypercortisolaemia itself, reverses on recovery. (29) Suppression of cortisol secretion occurs normally via glucocorticoid receptor-mediated inhibitory feedback to the hypothalamus it is readily produced by dexamethasone, which is a potent exogenous glucocorticoid (the...

Adipose tissuederived proteins

Leptin Leptin was first characterized in 1994 (Zhang et al. 1994) and is one of the most important adipose tissue-derived hormones (Stanley et al. 2005). Leptin is the product of the ob gene which is predominantly expressed in adipocytes (Zhang et al. 1994), but also in gastric epithelium (Bado et al. 1998) and placenta (Masuzaki et al. 1997). The name 'leptin' has its roots in the Greek word 'leptos', meaning thin, and leptin was initially viewed as an adipocyte-derived signal that functions primarily to prevent obesity (Flier 2004). Indeed, the effects of leptin on energy homeostasis are well documented exogenous leptin administration, both centrally and peripherally reduces food intake and increases energy expenditure (Friedman and Halaas 1998 Rosenbaum and Leibel 1998 Kershaw and Flier 2004). Adipocytes secrete leptin, however, in direct proportion to adipocyte size, and the majority of obese animals and humans have increased plasma leptin instead of an absolute or relative leptin...

Acute Stressinduced Changes in Blood Leukocyte Numbers Contradicting Results or a Biphasic Response

Short duration stress (order of minutes), mild psychological stress, or during exercise. In contrast, stress conditions that result in the activation of the HPA axis induce a decrease in circulating leukocyte numbers. These conditions often occur during the later stages of a stress response, long-duration acute stressors (order of hours), or during severe psychological, physical, or physiological stress. An elegant and interesting example in support of this hypothesis comes from Schedlowski et al. who measured changes in blood T cell and NK cell numbers as well as plasma catecholamine and cortisol levels in parachutists (Schedlowski et al., 1993a). Measurements were made 2h before, immediately after, and 1h after the jump. Results showed a significant increase in T cell and NK cell numbers immediately (minutes) after the jump that was followed by a significant decrease 1 h after the jump. An early increase in plasma catecholamines preceded early increases in lymphocyte numbers,...

Stressresponsive hormones

Stress-responsive hormones, including but not limited to adrenal corticosteroids and catecholamines, have a myriad of effects on various aspects of the immune response in both down- and upregulatory fashion.(23) Often hormones affect immunity in an 'inverted U-shaped' way, being suppressive at either abnormally high or abnormally low levels. As mentioned above, the hypothalamic-pituitary-adrenal axis, itself triggered by immunological as well as psychological events, is immunoregulatory, and both corticotrophin-releasing factor and ACTH have direct effects on immunity in addition to those via induction of release of cortisol. Growth hormone increases T- and NK-cell functions in aged animals. Prolactin antagonizes glucocorticoid-induced immune suppression. Gonadal hormones affect immunity. NK cell activity is higher in the luteal phase of the menstrual cycle (which should influence surgeons in the timing of cancer surgery in premenopausal women). Cellular immunity is depressed during...

Influence of products of the immune system on the central nervous system

The immune system affects brain and behaviour, especially via the effects of immune cytokines on the central nervous system.(42) Although cytokines are relatively large molecules, some, particularly IL-1, can cross the blood-brain barrier via active transport. IL-1 is also produced in the brain by both microglia, which are macrophages resident in the central nervous system, and astrocytes. Peripheral IL-1 can affect the brain, including its production of cytokines, via stimulation of the vagus afferent fibres. There are cytokine receptors in the brain, including those for IL-1, IL-8, and interferon, on both glial cells and neurones. Cytokines play a role in the development and regeneration of myelin-producing oligodendrocytes. Brain cytokines play a role in immune effector mechanisms as regulated by the brain, including a role in brain infection and inflammation. Cytokines are relevant to the progression of multiple sclerosis, gliomas, HIV-associated dementia, brain injury, and...

Emotions and affective style

The idea that the two cerebral hemispheres make different contributions to the development of dysphoric emotions (e.g. depression, anxiety) has attracted considerable attention in the past few years. Evidence for this idea comes from two separate research lines. The first is exemplified by the experimental work of Hugdahl,( 3) who directly manipulated hemisphere information processing (e.g. by confining visual stimuli to one visual field hemisphere) in order to examine the differential involvement of the two hemispheres in emotional reactions. His studies indicate that fear-relevant stimuli (e.g. pictures of snakes) evoke a cardiac defence reaction when they are flashed to the right hemisphere (i.e. left visual field) of healthy subjects, but not when they are flashed to the left hemisphere (i.e. right visual field) of these subjects. Also, the two hemispheres of normal subjects apparently differ in their conditionability. That is, when visual stimuli flashed to either the right or...

Psychophysiological parameters

Recent animal studies suggest that there are conditions in which peripheral parameters may act as the determinants of central dysfunctions. An interesting example is provided by cortisol. Exposure to aversive events mobilizes the hypothamalamic-pituitary-adrenal axis, which results in an increased secretion of cortisol. High levels of cortisol may have neurotoxic effects on hippocampal circuits, thereby producing memory impairments. These findings may elucidate some clinical features of depression and post-traumatic stress disorder. Both conditions are associated with stress and memory disturbances, and there are some preliminary indications that at least some patients with these disorders have a reduced hippocampal volume. (59

Physician as Catalyst

That allegedly controls the body's Cortisol levels, thereby suppressing appetite, which the promoters claim results in weight reduction. Another product, marketed in San Antonio, Texas, was a liquid solution taken at 8 pm, with nothing to eat after that time. It reportedly burned away the fat while the consumer slept. An individual told me she had tried this product four times without success and asked me what she was doing wrong. I told her that her lack of success was due to the fact that the product did not work. Even the medical community has contributed to the magic pill myth. For years physicians have written prescriptions for various obesity medications, typically with poor results. If any one medication was the magic pill for obesity, there would be no overweight physicians. Pharmacotherapy can be a useful adjunct to dietary control and behavior change, but it can never be the primary treatment. Chapter 6 will discuss phar-macotherapy in more depth.

Mechanism Of Vitamin A Action

RA and its isomer, 9-ds-retinoic acid (9cRA), serve as ligands that activate ligand-activated transcription factors that belong to a superfamily of nuclear receptors.10 This superfamily of related genes expresses nuclear receptors for steroids (the female sex hormones estrogen and progesterone, the mineralocorticoid aldoster-one, the glucocorticoid cortisol, the male sex hormones testosterone and dihy-drotestosterone), prostanoids, the thyroid hormone, the hormonal form of vitamin D, calcitriol, and peroxisome proliferators. Additionally, more than 50 orphan receptors belong to this family. Two classes of retinoid receptors occur retinoic acid receptors (RAR) and retinoid X receptors (RXR). Each has three different versions (a, p, and y) encoded by distinct genes. Each version also has multiple isoforms resulting from differential promoter use and alternative RNA splicing. Thus, multiple forms of each occur (e.g., RARa1, RARa2, etc.). Moreover, RAR functions as a heterodimer with RXR....

The Role Of Hormonal Replacement

Following induction of brain death in the experimental animal, a rapid reduction of plasma free T3, Cortisol and insulin was described. This clearly indicated the need to assess the impact of hormonal replacement in organs used for transplantation and on the body as a whole. In a study done in pigs T3 (2 mcg), cortisol

Pathogenesis and Pathophysiology

Growth hormone and Cortisol, all of which have well-described metabolic actions. The metabolic actions of cytokines are in general not so well understood and it is possible that many of these actions are mediated by hypothalamo-pituitary activation and subsequent elevation of catabolic hormones.

Hypothalamic PituitaryAdrenal Axis and Glucocorticoid Responses

The endogenous glucocorticoid in man is cortisol, whereas in rodents it is corticosterone. The expression of corticotrophin releasing hormone (CRH) in the hypothalamic region of the brain is activated by inflammatory or other stimuli. In turn, CRH stimulates the release of adrenocorticotropin hormone (ACTH) into the bloodstream from the anterior pituitary gland. ACTH then stimulates the synthesis and release of glucocorticoids from the adrenal glands. In order to maintain regulation of this axis, glucocorticoids feed back and downregulate the HPA axis at the level of the hypothalamus and pituitary. In addition to regulation of the immune system, glucocorticoids are also essential for the regulation of several homeostatic systems in the body, including the central nervous system, cardiovascular system, and metabolic homeostasis. Glucocorticoid regulation of the immune system will not be discussed in detail here but has been the subject of another recent review (Webster...

Multiple systems organ failure

Although abnormalities of liver blood tests are the most obvious manifestation of multiple systems organ failure, there is increasing evidence of a wide range of more subtle changes in hepatocellular metabolic function that may be of profound prognostic importance. The initial response to sepsis is associated with increased gluconeogenesis and a reprioritization of hepatic protein synthesis. The former is driven in part by increased glucose counter-regulatory hormones (cortisol, glucagon, and epinephrine (adrenaline)), but increased uptake of alanine for gluconeogenesis is also important. In bacteremic burns patients, hepatic glucose output doubled and alanine uptake by the liver rose fivefold. Protein anabolism and catabolism both increase, with peripheral release of amino acids available for hepatic uptake and acute phase protein synthesis. This enhanced acute phase protein synthesis and concomitant reduction in albumin synthesis is mediated by the release from Kupffer cells of a...

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Further evidence for disruption of the 5-HT system comes from blunted neuroendocrine responses (Cortisol and prolactin) to D-fenfluramine in former users of the drug. A study of former users(22) suggested associated personality traits of novelty seeking, depression, and aggressive-impulsive behaviour. The frequency of polysubstance abuse in this population confounds these findings, and the direction of causality in the neuroendocrine, neurochemical, and personality findings is uncertain. Krystal et al.'(23) have shown mild to moderate impairment on subtests of the Weschler Memory Scale in nine users, none of whom met clinical criteria for affective disorder. Positron emission tomography studies using novel 5-HT ligands have found results compatible with a decrease in a structural component of brain 5-HT neurones 24' However, most studies have been of polysubstance users and rely on self-reported histories of drug use, and the control groups were not matched for use of other substances.

Anthrax Lethal Toxin Repression of GR

One unanswered question has been the role of HPA axis glucocorticoid responses during exposure to anthrax lethal toxin. As we have previously described, an intact HPA axis response is essential for survival from a range of proinflammatory, bacterial, and viral insults.We have recently shown that adrenalectomy also enhances sensitivity to LeTx in all mouse strains tested including DBA 2J mice, which are completely resistant to LeTx when the adrenals are intact (Moayeri et al., 2005). However, unlike the studies described earlier, dexamethasone treatment does not prevent this increased mortality rate but rather sensitizes mice to LeTx (Moayeri et al., 2005). Although this data is contrary to what one might initially expect, there is data to demonstrate that the HPA axis needs to be carefully balanced for optimal host responses in bacterial exposures. Perturbations in either direction are detrimental to health. Indeed, prolonged treatment of septic shock with high doses of...

Adrenal glucocorticoids in critical illness

Corticotropin-releasing hormone from the paraventricular nucleus is carried in the hypophyseal-portal circulation and stimulates release of ACTH from the anterior pituitary. The result is an increase in plasma cortisol levels with a loss of the normal circadian rhythm. During this period of sustained and increased cortisol synthesis there may be a reduction in the production of other adrenal steroid hormones. Conversely, adrenal insufficiency during critical illness is being reported more frequently, particularly in cases of systemic sepsis with shock.

Introductory Comments

The relationship between obesity and cardiovascular disease is well established and has been extensively reviewed.1-4 The coexistence of obesity and hypertension provides a compelling rationale to examine specific mechanisms that contribute to obesity and evaluate whether these mechanisms explain the relationship between blood pressure (BP) and increased levels of body fat. The discovery of leptin, an adipocyte-derived hormone, in 19945 marked the beginning of rapid progress in understanding signals involved in responding to nutritional input, central pathways regulated by these signals, and efferent mechanisms regulated by leptin and these signals. Because human obesity is a disease of elevated leptin levels, the purpose of this review is to examine the evidence testing the hypothesis that increased leptin levels contribute to elevated BP in obesity.

Stress and REMS Role of PRL

There are different possible explanations for a parallel increase in PRL and REMS after stress. One possibility is the relationship between PRL and CRH. CRH is responsible to regulate the stress response through of adrenocorticotropic hormone (ACTH) release, which in turn regulates cortisol production (Menzaghi, Heinrichs, Pich, Weiss, and Koob 1993). Some studies have been demonstrated that CRH induces PRL release during stress conditions (Akema et al. 1995 Morel et al. 1989), and that the i.c.v injection of alpha-helical 9-41 a CRF-receptor antagonist before stress by immobilization in rats abolished REMS rebound after stress (Gonzalez and Valatx 1997 Garc a-Garc a 2000). These results suggest that PRL could be modulating REMS increase after stress via CRH.

General Consideration on the 5aReductases

As previously mentioned, all steroids possessing a A4-3keto structure (androgens, PROG, and adrenal steroids) are substrates for the 5a-R, although with different affinities. For both isozymes (see next section), in the rat and in humans, the Kms for the main circulating representatives of the different classes of hormonal steroids rank in the following order P T corticosterone cortisol.

Biological vulnerability

The search for evidence of biological indices has up to now been focused on the kinds of markers that have been studied in depressed adults, such as abnormalities of cortisol physiology (Casat & Powell, 1988), melatonin (Shafii et al., 1996), thyroid-hormone levels (Dorn et al., 1996 Kutcher et al., 1991), sleep (Emslie et al., 1987), and brain imaging (Steingard et al., 1996). Several studies have shown that, in comparison with non-depressed patients, depressed young people are less likely to show suppression of cortisol secretion when the exogenous corticosteroid dexamethasone is administered (Casat & Powell, 1988) and more likely to have sleep abnormalities (Appelboom-Fondu et al., 1988 Cashman et al., 1986 Emslie et al., 1987 Kutcher et al., 1992 Lahmeyer et al., 1983 Riemann & Schmidt, 1993). There has been very little longitudinal research on most of these measures. There is, however, some evidence that cortisol levels predict subsequent depression. Goodyer and colleagues...

Structure and Biochemical Properties of the 5aReductase Isozymes

Of the enzymatic proteins, determined from their respective cDNAs, show a limited degree of homology (about 47 ), and a predicted molecular weight of 28-29 kDa. The homology between the human and rat enzymes is 60 for the type 1, and 77 for the type 2 isozyme. The monkey isoforms are structurally and functionally more similar to their respective human counterparts. In terms of primary structures, both isozymes are composed of a high number of hydrophobic aminoacid residues, distributed throughout the molecule this strongly imposes the localization of the enzymes in cell membranes (see this section). Consensus sequences for the binding of substrates similar to those present in other reducing enzymes have not been found in either isozyme, but mutational analysis has permitted to localize the region of substrate binding in the N-terminal portion of the protein, which is encoded by the first exon the binding site for NADPH, the cofactor of the 5a-R, appears to be located in the C-terminal...

The Effect of PPARs on Fatty Acid Transport Proteins 6531 Membrane Fatty Acid Transport Proteins

In general, PPARa and its concomitant ligands have been implicated in the regulation of many genes involved in hepatic lipid metabolism and energy homeostasis.122,124,131 These include both mitochondrial and peroxisomal P-oxidative enzymes as well as fatty acid synthetase and lipoprotein assembly and transport proteins.124,132 PPARy has been associated primarily with lipolytic effects and is known to regulate enzymes involved in adipocyte differentiation and lipid storage and metabolism, for example, LPL and acyl-CoA synthetase, as well as the hormone leptin.122,124,133

Biological Markers in Croatian War Veterans with Combat Related Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a severe psychiatric illness associated with disturbances in diverse neurobiological systems. The evaluation of a variety of biomarkers might facilitate a goal of modern medicine, a proper treatment for an individual patient at a given stage of disease. This is especially important in PTSD, a disorder with a complex clinical picture, diverse symptoms, and frequent comorbidities. Biological markers (platelet serotonin, platelet monoamine oxidase, plasma lipid levels, plasma dopamine beta hydroxylase, plasma cortisol and serum levels of thyroid hormones) were determined, and clinical symptoms were evaluated, in 93 male war veterans with chronic combat related PTSD, using the Clinician Administrated PTSD Scale, Positive and Negative Syndrome Scale, and the Hamilton Rating scales for Depression and Anxiety. Platelet serotonin concentration and plasma dopamine beta hydroxylase activity were similar in PTSD subjects and healthy controls....

Benefits Of Continuous Positive Pressure Therapy

In addition, CPAP produces many other sustained benefits that may have significant impact on long-term health outcomes, in particular, those processes that appear to contribute to the pathogenesis of cardiovascular disease. These benefits include decreased platelet activity and aggregation during sleep in OSA patients (32), a decrease in factor VII coagulant activity (VII C) (32,33), decreased fibrinogen levels (34), increased levels of circulating nitric oxide (35,36), decreased overall sympathetic nervous system output (37,38), improved insulin sensitivity and glucose intolerance (39), reduced C-reactive protein (CRP) and interleukin-6 levels (40), and reduced serum leptin levels (41,42).

Pathophysiology of malnutrition

Obesity is a specialized form of malnutrition that is becoming increasingly common in children, raising concerns about type 1 diabetes, cardiovascular disease, and risk of cancer. A recent study has reported that low-grade inflammation, as determined by serum levels of high-sensitivity C-reactive protein, while significantly increased in children with type 1 diabetes, a high level was even more pronounced in apparently healthy juveniles with primary obesity 19 . Uncomplicated morbid obesity in adolescents may be accompanied by alterations in the levels of circulating T cells and cytokine response 20 . Other studies show that regulation of natural killer (NK) function and proliferative response to mitogens in vitro are affected 21, 22 . Leptin, the product of the ob gene, is a pleiotropic molecule that regulates food intake through metabolic and neuro-endocrine functions, has cyto-kine-like activities and is a major regulator of immune function 23 . Leptin is acutely increased during...

The liver and nutrient metabolism

The liver performs over 500 metabolic functions. In fact, the metabolic activity of the liver accounts for 20-30 of the oxygen consumption and energy expenditure of the body 3 . When liver dysfunction occurs, a catabolic state is induced, and increased serum levels of insulin (often with insulin resistance), glucagon, epinephrine and cortisol are present. Because the liver is involved in the metabolism of all nutrients (Table 4.1), an alteration of liver function causes a concomitant alteration in nutrient metabolism and storage.

The Association Between Obesity And Type 2 Diabetes

Several mechanisms have been proposed to explain how excessive body weight is associated with Type 2 diabetes. In general, the accumulation of fat mass is associated with a decline in whole body insulin sensitivity. The distribution of obesity is important, with resistance to the action of insulin and glucose intolerance most closely associated with excess abdominal adipose tissue. As visceral adipose tissue increases plasma triglyceride (TG) concentrations are elevated, high-density lipoprotein (HDL) cholesterol decreases and low-density lipoprotein (LDL) cholesterol increases with a greater proportion of the more atherogenic small dense LDL particles (LDL subclass III). Other associated characteristics include an elevated plasma non-esterified fatty acid (NEFA) concentration, an increased plasminogen activator inhibitor 1 (PAI-1) concentration, hyperuricaemia and hypertension. Abdominal obesity is also associated with specific changes in skeletal muscle morphology, namely a...

The importance of multicomponent interactions

Physiological changes themselves, as may stem from a major life stress (such as loss of one's job), can interact, as, for example, the discovered interactions between the endocrine and immune systems, each of which can affect neurotransmitter systems and mood (Anisman & Merali, 1999). Physiological processes also affect cognitive processes. For example, increasing levels of cortisol (a stress hormone) tend to focus attention on threats and negative events animals with high cortisol are more sensitive and attentive to possible threats than low-cortisol animals (Rosen & Schulkin, 1998 Toates, 1995), and, as we will note below, people from abusive backgrounds have high levels of cortisol. In a major review, Taylor et al. (2000) explored how differences in gender evolution and sex hormones can differently affect stress and depression in the genders. They called for greater gender-sensitive research.

Depression And Stress

We can make a start at integration by focusing on that well-known but tricky concept, stress. The simple reason for this is that there is little doubt now that major depression is a state of chronic stress as measured by subjective reports, life events (Morriss & Morriss, 2000), physiological indicators of autonomic nervous system hyperarousal (Toates, 1995), and overactivity of the hypothalamic-pituitary-adrenal (HPA) system, which results in high cortisol levels, called hypercortisolaemia (Levitan et al., 2000 McGuade & Young, 2000 Nemeroff, 1998 Raadsheer et al., 1994). Importantly, hypercortisolaemia has many detrimental effects on the immune system (Maes, 1995), and various internal organs and brain areas (Sapolsky, 1996,2000), and by feedback interactions itdowngrades 5-HT, an important neurotransmitter in mood regulation (McGuade & Young, 2000). There is good evidence that even in the less severe depression of dysthymia there are significant physiological disturbances of...

Stress Hormonal Change Cytokines and Sleep Behavior

Note that acute stress produces rapid changes in serum cortisol levels, while the effect of sleep deprivation produces changes in a much slower fashion (Weitzman, Zimmermann, Czeisler, and Ronda 1983). Furthermore, it is generally believed that in animal models sleep loss may be more stressful than in humans, and significant alterations in immunity have been reported in sleep deprived mice (Toth and Rehg 1998), a feature which we were unable to replicate in the model described. A dissociation between cytokine changes and cortisol levels was also reported in human subjects following exposure to low levels of endotoxin (Mullington et al. 2000). Other groups have addressed the relationship between sleep disruption, cortisol levels and cytokines (Rogers 2001 Vgontzas et al. 2002), while the role of IL-1 as a mediator of these interactions, in particular in an elderly human population, has also been studied (Prinz, Bailey, and Woods 2000). One such study concluded that the (activated) HPA...

Neuroendocrine and metabolic effects

The neuroendocrine stress response after painful trauma is characterized by an increased secretion of catabolic hormones (ACTH, cortisol, glucagon, catecholamines) and a decreased secretion of anabolic hormones (insulin, testosterone, growth hormone). This results in hypermetabolism and release of substrates (glucose, amino acids, fat) from peripheral stores (muscle, fat tissue, liver). Hyperglycemia, increased protein breakdown, and a negative nitrogen balance are the consequences. In addition, the release of aldosterone and vasopressin is enhanced and results in sodium and water retention. Nociceptive impulses from the injured area contribute significantly to the initiation and maintainance of these effects, since regional anesthesia can potently reduce the stress response ( Keh.le.t.,,1 9.9.3). Other factors such as cell breakdown products or inflammatory mediators also play a role. Stress-induced activation of the hypothalamopituitary axis may cause suppression of immune functions...

The endocrine system in critical illness

The circulating levels of ACTH-cortisol, thyroid-stimulating hormone-thyroxine, epinephrine (adrenaline), norepinephrine (noradrenaline), vasopressin, growth hormone, prolactin, insulin, and glucagon all increase in severe illness. These changes represent an exaggeration of normal host responses. There then develops a reduced thyroxine response to thyroid-stimulating hormone and a reduced synthesis of insulin-like growth factors in response to growth hormone. It is not clear at present of the significance of this tissue resistance or of the benefit of treating these derangements.

Hypothalamicpituitaryadrenal axis

The best known neuroendocrine response to injury is undoubtedly the increase in ACTH secretion and the resultant increase in adrenocortical secretion of glucocorticoid hormones. It is obvious that this increase is of great importance. In its absence, tolerance to stress is reduced. In critically ill patients cortisol levels are positively correlated with APACHE, TISS (therapeutic intervention scoring system), and ISS (injury severity score). In patients suffering myocardial infarction cortisol levels reflect both infarct size and mortality. There are also significant associations between burn size and cortisol levels. Recently the hypothalamic-pituitary-adrenal axis was found to undergo a biphasic change during critical illness. In the first phase, lasting a few days, the high cortisol concentrations appear to be induced by augmented ACTH release. In the second phase there is a discrepancy between low ACTH and high cortisol concentrations, suggesting that cortisol release is...

Influence of anesthesia on the endocrinemetabolic response to surgery

Stress-induced changes in pituitary hormones are blocked or inhibited by regional anesthesia with local anesthetics. Thus the normal increase in plasma ACTH, b-endorphin, vasopressin, prolactin, and growth hormone is not observed, while the minor decrease in follicle-stimulating hormone and luteinizing hormone in female patients is accelerated. Thyroid-stimulating hormone changes appear to be unaffected. The cortisol response to procedures on the lower part of the body is blocked by regional anesthesia, and correspondingly changes in aldosterone and renin are generally diminished. The increase in epinephrine and norepinephrine is blunted. The hyperglycemic response to surgery, considered to be due to a combination of increased glycogenolysis and insulin resistance, is reduced or blocked by regional analgesia. This is not mediated by inhibition of a single hormonal response to trauma but probably through the simultaneous inhibition of the cortisol, catecholamine, glucagon, and growth...

Asymptomatic hyponatremia

Active therapy with hypertonic NaCl is not indicated in patients with asymptomatic hyponatremia. If the patient is volume depleted, isotonic (154 mmol l) NaCl is usually the fluid of choice, and if there is a hormone deficiency (cortisol, aldosterone, thyroid hormone) appropriate replacement is indicated. If the patient has received a drug which may interfere with renal handling of sodium or water, it should be discontinued whenever possible. Water restriction is of theoretical benefit in selected disorders, but practical considerations limit its usefulness. With successful fluid restriction (less than 800 ml day), correction of plasma sodium by more than 1.5 mmol l daily cannot be expected. Thus water restriction is only appropriate in a patient whose hyponatremia is asymptomatic.

The Hypothalamus PituitaryAdrenal Axis

Glucocorticoid hormones (cortisol in humans and corticosterone in rodents) are the final step of the activation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the major systems implicated in responding to environmental modifications. Activation of the HPA axis is determined by brain inputs to the hypothalamus, which releases corti-cotropin-releasing hormone (CRH) CRH reaches the hypophysis via the hyphophyseal portal system and activates the release of ACTH in the bloodstream, which, in turn, triggers the secretion of glucocorticoids by the cortical part of the adrenal gland (for review, see ref. 1). The secretion of glucocorticoids is characterized by a circadian cycle. Concentrations of these hormones are low during the inactive phase (dark phase in humans and light phase in rodents) and rise during the first hours that precede the active phase (2). The secretion of glucocorticoids is also activated by practically all forms of stress, which induces a rapid and large...

Biological Effects

The central effects of the natriuretic peptides are comparable to those in the periphery, i.e. augmentation of natriuresis and diuresis and modulation of salt and water homeostasis. Natriuretic peptides are specifically involved in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) system in man and rodents ANF inhibits the HPA system at all regulatory levels, while CNP stimulates the release of cortisol. The natriuretic peptides are also thought to play a role in higher brain functions. In rodents, ANF was found to reduce anxiety levels, whereas CNP induced the opposite effect. In patients with panic disorder, basal ANF plasma levels are lower in comparison to healthy volunteers, but ANF secretion is faster and more pronounced during experimentally induced panic attacks. Interestingly, panic anxiety and concomitant ACTH and cortisol secretion elicited by stimulation with cholecystokinin tetrapeptide were also attenuated by ANF infusions in patients as well as in healthy...

Diagnosis and clinical presentation

A blood glucose measurement is part of the initial investigation of any patient presenting with disorientation or coma. Diagnosis is made by the measurement of blood glucose using arterialized capillary blood from a fingerprick. Whole-blood glucose measured in this way will be 10 to 15 per cent lower than corresponding plasma samples. If hypoglycemia is found, blood should be drawn for plasma glucose in a fluoride or oxalate tube, together with plasma insulin, C peptide, and cortisol. To assist future diagnosis, samples should be taken before treatment is initiated. A low ratio of C peptide to insulin suggests exogenous insulin administration, whereas a normal ratio suggests an endogenous source of insulin.

Impaired renal water excretion

Mineralocorticoid deficiency impairs water excretion by mechanisms activated by a decrease in effective circulating volume. These include non-osmotic stimulation of ADH secretion and impaired renal free water generation owing to reduced distal fluid delivery in the kidneys. However, glucocorticoid deficiency is usually of primary importance, as cortisol replacement rapidly increases the rate of water excretion and raises the plasma sodium concentration to normal. Plasma levels of ADH are usually inappropriately elevated in glucosteroid-deficient patients and return to normal upon glucocorticoid replacement. Persistent ADH secretion in patients with glucocorticoid deficiency is probably due to a loss of hypotonic suppression of ADH release owing to glucocorticoid deficiency per se, which is aggravated secondarily by multiple non-osmotic stimuli such as nausea and hypoglycemia. Both sodium loss by mineralocorticoid deficiency and ADH-related retention of free water contribute to the...

Adrenal dysfunction in critical illness

Normal adrenal function is vital to survival from severe (septic) insults. Plasma cortisol concentrations increase during critical illness and this rise under conditions of stress appears to be a protective mechanism. In severe illness there is a relative shift in the metabolism of adrenal pregnenolone away from mineralocorticoid and adrenal androgen pathways and toward the glucosteroid pathway. Increased plasma concentrations of cortisol in critical illness reflect a balance between an increased cortisol secretory rate and a reduced (hepatic) degradation. Septic patients with hepatic disease may have higher cortisol levels than septic patients without liver disease ( Bouachour ei a 1995). A decreased level of corticosteroid-binding globulin a specific transport protein for glucocorticoids further increases free cortisol concentrations. Marked elevated cortisol concentrations 1995 .SonleLa 1995) and in patients in a general ICU (Jurney etal 1987). However, there is a wide range in...

Chapter References

Jurney, T.H., Cockrell, J.L., Jr, Lindberg, J.S., Lamiell, J.M., and Wade, C.E. (1987). Spectrum of serum cortisol response to ACTH in ICU patients. Correlation with degree of illness and mortality. Chest, 92, 292-5. Rothwell, P.M., Udwadia, Z.F., and Lawler, P.G. (1991). Cortisol response to corticotropin and survival in septic shock. Lancet, 337, 582-3.

Measures to control the effects of hyperthyroidism

Propranolol (80 mg orally or 1-2 mg intravenously as required) blocks the b-adrenoreceptor effects of thyroxine and is particularly useful for reducing sinus tachycardia. It also impairs conversion of thyroxine to tri-iodothyronine and inhibits release of thyroid hormone. Propranolol is contraindicated in patients with cardiac insufficiency or air-flow limitation, although newer more specific b-blockers such as atenolol can be used in patients with congestive cardiac failure, bronchospasm, or peripheral vascular disease. Rapid atrial fibrillation should be managed by standard protocols involving digoxin administration (up to 1.5 mg as a loading dose) following correction of hypokalemia and anticoagulation. Thyrotoxicosis accelerates the metabolism of digoxin. Conversely, patients with thyrotoxicosis are more sensitive to warfarin because vitamin-K-dependent clotting factors are metabolized more rapidly. Verapamil may also be useful in this setting to reduce the ventricular rate....

Diagnosis of myxedema coma

Tri-iodothyronine, free thyroxine, and cortisol. The diagnosis is positive when the results are in agreement with primary hypothyroidism, i.e. elevated plasma thyroid-stimulating hormone and dramatic reduction of both free tri-iodothyronine and free thyroxine, thus excluding a 'euthyroid sick syndrome' or low

Psychological Stress and Immunity

Stress can be defined as a state of altered homeostasis resulting from either an external or an internal stimulus. The host's response to stress is designed to restore homeostasis through a variety of adaptive neuroendocrine-mediated mechanisms (Ramsey, 1982). This restoration of homeostasis is accomplished, in part, through the increased synthesis of a variety of neuroendocrine-derived peptides and hormones. For example, the perception of a psychological stressor activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic branch of the autonomic nervous system. This activation culminates in the synthesis of both cortisol (corticosterone in rodents) by the adrenal glands and epinephrine and norepinephrine by the sympathetic nervous system. Interestingly, in addition to their roles in maintaining homeostasis, these and other products of the nervous and endocrine system pathways can also modulate immune function through their binding to specific receptors that are...

Fat metabolism in the healing wound

The healing process for most wounds requires an increase in caloric intake over basal levels. This is especially true in severely injured, burned, or critical patients in whom the stress response has placed them in a hypermetabolic state.82,83 Induction of the stress response via the hypothalamus is initiated by proinflammatory cytokines and results in increased levels of the stress hormones (e.g., glucagon, cortisol, and catecholamines). These hormones then result in a protein-catabolic state as well as The previously mentioned endocrine function of WAT may also play a role in wound metabolism during the early stages of wound healing. Leptin production increases during inflammation.47 Interestingly, leptin activity has been detected in the fluids of experimental wounds in pigs during the first few days following injury,105 and it was suggested by the authors that this hormone may function in an autocrine and paracrine manner during wound healing. The significance and role of leptin...

Circadian sleepwake rhythms

The suprachiasmatic nucleus also controls other biological rhythms including body temperature and cortisol production with which the sleep-wake rhythm is normally synchronized. In contrast, growth hormone in adults is locked to the sleep-wake cycle and is released with the onset of SWS, whatever its timing.

Other medical conditions

The neurological manifestations of African sleeping sickness (trypanosomiasis) are characterized by delusions, hallucinations, personality changes, and reversal of sleep-wake rhythm. The patient remains somnolent in the daytime and progresses gradually into the stage of stupor or coma. Disruption of the circadian sleep-wake rhythm is the most prominent finding in polysomnography. Circadian disruption of plasma cortisol, prolactin, and sleep-wake rhythms are noted in the most advanced stages, and these findings suggest selective changes in the suprachiasmatic nucleus. The diagnosis of trypanosomiasis is based on history and confirmation of the organism in the blood, bone marrow, cerebrospinal fluid, lymph-node aspirates, or a scraping from the chancre.

Inadequate Sleep and Disease

An ever-growing number of studies have been performed in order to assess the impact of inadequate sleep on the quality of life, morbidity and mortality. For instance, a retrospective study conducted in Denmark demonstrated that nighttime-working women showed augmented risk for breast cancer than daytime-working women (Hansen 2001). Likewise, increased risk for infections was reported by workers whose working hours were comprised to the night, when compared to daytime workers (Mohren, Jansen, Kant, Galama, van den Brandt, and Swaen 2002). This is somehow an expected outcome, given that shift workers experience a complete alteration of circadian rhythm of some hormones, such as cortisol and melatonin, in addition to temperature (Fujiwara, Shinkai, Kurokawa, and Watanabe 1992 Hennig, Kieferdorf, Moritz, Huwe, and Netter 1998 Vangelova 2000). In an elegant in vitro study, Rogers, van den Heuvel, and Dawson (1997) evaluated the influence of cortisol and melatonin on human lymphocyte...

Effects of noise on patients

Resting persons primarily exhibit peripheral vasoconstriction and an increase in diastolic blood pressure after a sound pressure level of 70 dB(A), whereas systolic pressure is barely affected and the heart rate is lowered. No constant change in catecholamine or cortisol levels can be documented. Alarms exceeding 90 dB(A) provoke a startle response.

Non24Hour Sleep Wake Disorder

There are several reports of successful entrainment of circadian rhythms of individual blind human subjects by MLT treatment. These include in single subjects, synchronization of a disturbed sleep-wake cycle (5 mg) (3), advancing sleep onset, stabilizing sleep and reducing day time naps (5 mg) (58) and entrainment (7.5 mg) (57). In the first subject (3), the free-running rhythms in both temperature and urinary cortisol were on further analysis found not to be entrained (22) whereas in the third subject (57) entrainment of the endogenous MLT rhythm was demonstrated, indicating true entrainment of the underlying circadian pacemaker. In a blind, retarded boy with Non-24-Hour Sleep Wake Disorder, MLT corrected sleep phase (43).

Radiographic and Other Studies

Rarely helpful in the acute setting but may help identify underlying abnormalities responsible for hypokalemia. Abdominal ultrasound or CT scan may help identify adrenal tumors, and MRI scan of the brain may identify pituitary abnormalities associated with increased cortisol release. These studies should be performed based on an index of suspicion from history and laboratory results.

Treatment Of Acute Exacerbation Of Ms

The Cochrane systematic review provides quantitative evidence favouring ACTH or methylprednisolone against placebo for treating acute exacerbations in patients with MS. In the various trials, benefit is seen in the form of quicker recovery and lowering of mean disability score at 1 week and 4 weeks. With respect to ACTH, it was postulated that adrenal steroids other than cortisol or possibly a direct effect of ACTH on neural tissue was responsible for a therapeutic effect. The subsequent endocrine work suggested that the cortisol response to ACTH is not consistently reproducible, may not be prompt, and endogenous steroid production may never reach the range generally recommended for autoimmune diseases. Besides, ACTH is hardly used to treat any systemic disease of presumed autoimmune etiology. The majority of neurologists use IV methylprednisolone for the treatment of a relapse of MS.

Endocrinological Factors Hormones

There are a few other hormonal factors that change during pregnancy and are involved in the sleep process. During pregnancy, corticotropin-releasing hormone (CRH), which is normally synthesized by the hypothalamus, is synthesized by the placenta, fetal membranes and decidua and is physiologically identical to that of the mother (Florio, Cobellis, Woodman, Severi, Linton, and Petraglia 2002 Wadhwa, Sandman, Chicz-DeMet, and Porto 1997). CRH is a crucial element in parturition and fetal growth and varying levels have been shown to be involved with preterm labor (Inder et al. 2001 Siler-Khodr, Forthman, Khodr, Matyszczyk, Khodr, and Khodr 2003 Wadhwa et al. 1997). Prolactin is a hormone produced by the anterior pituitary gland with its primary role being initiation and sustenance of lactation. The secretion of prolactin is increased by stress and is dependent upon a woman's estrogen levels. Finally, cortisol, a well-known steroid hormone, is particularly involved in the pregnancy...

Metabolic systems hepatic pancreas endocrine

Experimental work has suggested that many patients with SIRS may have relative deficiency of cortisol. This is often only demonstrated by a direct challenge with a synacthen (ACTH stimulation) test. Resistant hypotension, elevation of blood potassium, and a fall of blood sodium may also indicate hypoadrenalism.

The Immune Response To Infection Injury And Inflammatory Agents

The immune system has a large capability for immobilizing invading microbes, creating a hostile environment for them, and bringing about their destruction (1). The immune system may also become activated, in a similar way to the response to microbial invasion, by a wide range of stimuli and conditions that do not directly involve pathogens these include burns, penetrating and blunt injury, the presence of tumor cells, environmental pollutants, radiation, exposure to allergens, and the presence of chronic inflammatory diseases. The response of the immune system to this diverse range of agents and conditions contains many common elements. These, however, vary in intensity according to their impact on the body. The elements of the response include the production of immunomodulatory proteins (cytokines), oxidant molecules (hydrogen peroxide, superoxide, hypochlorous acid, and nitric oxide), anti-inflammatory hormones (cortisol), natural antagonists (cytokine receptor antagonists), and...

Mechanism of action

In the severely depressed patient, the adrenal glands produce too much cortisol. In turn, the high levels in the blood disrupt the normal diurnal rhythms of other glandular discharges, and the glands do not respond to the usual feedback mechanisms. The most prominent features of depression failure to eat, loss of weight, inability to sleep, loss of interest in sex, inability to concentrate thoughts, and difficulties in memory are distortions in functions regulated by the adrenal glands acting interdependently with the pituitary and hypothalamic cells, in a self-adjusting feedback. (70) Each seizure stimulates the hypothalamus to discharge its hormones, which cause the pituitary gland to discharge its products, which then affect the level of cortisol. The first effects of this cascade of events are transitory, but repeated seizures restore the normal interactions of the hypothalamic-pituitary-adrenal axis hormones. Feeding and sleep become normal motor activity, mood, memory, and...

Dennett development and design

This speculation has been amply supported by subsequent research. Studies of the effects of early post-natal separations on the regulation of cortisol in rodents have shown that persistent alterations in neuroendocrine can be caused by discrete periods of maternal separation (Sanchez et al. 2001). Furthermore these alterations are accompanied by behavioural changes. Huot et al. (2001) found that early post-natal separation was associated in rats with later preference for alcohol (ethanol) mediated via altered corticosteroid responses to stress. The mechanisms are complex and are likely to involve gene expression, and altered density of neurones in structures such as the hippocampus. It seems then that the wiring might be influenced by organism-environment interaction through a process that is similar to learning. If we are to

Other hormonal responses during aerobic exercise

Hormone and Cortisol are secreted in response to exercise, rising in concentration in the plasma gradually over the first 30 minutes to 1 hour (Fig. 8.12) - i.e. these are relatively slow responses, and are likely to be involved particularly in the release of stored fuels during prolonged exercise. The plasma glucose concentration may rise or fall during exercise (discussed below), but the insulin concentration falls somewhat during endurance exercise (Fig. 8.13). This represents a-adrenergic inhibition of its secretion from the pancreas, brought about by the increased circulating adrenaline concentrations. Glucagon secretion may also increase, although this is not a major change except with very strenuous, prolonged exercise. The increase in adrenaline, glucagon, growth hormone and cortisol concentrations is a typical 'stress' response (see Fig. 7.6). Since the major effects of glucagon are on the liver, and liver metabolism may not be dominant during exercise because of restricted...

Obesity and Type 2 Diabetes

A common feature of obesity, insulin resistance, and T2D is chronic, low-grade inflammation (Dandona, Aljada, and Bandyopadhyay 2004 Dandona, Aljada, Chaudhuri, Mohanty, and Garg 2005 Weisberg et al. 2006 Weisberg, McCann, Desai, Rosenbaum, Leibel, and Ferrante 2003 Wellen and Hotamisligil 2005). Markers of chronic subclinical inflammation (e.g., C-reactive protein and IL-6) are closely linked to insulin resistance and obesity (Finegood 2003 Temelkova-Kurktschiev, Henkel, Koehler, Karrei, and Hanefeld 2002). In addition, proinflammatory cytokines such as TNF-a, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-8, and macrophage inflammatory peptide (MIP)-1aare often increased in patients with obesity, insulin resistance and T2D (Gerhardt, Romero, Cancello, Camoin, and Strosberg 2001 Mohamed-Ali et al. 1997 Sartipy and Loskutoff 2003 Takahashi et al. 2003 Uysal, Wiesbrock, Marino, and Hotamisligil 1997 Weisberg et al. 2003, 2006 Xu et al. 2003 Yudkin, Kumari, Humphries, and Mohamed-Ali...

Impact Of Brain Death On The Heart

Brain death has damaging effects on the cellular and subcellular level of the myocardium.49 Myocardial preservation, therefore, begins with proper donor management and manipulation of the deranged neurohormonal milieu consequent to brain death. As early as 1954 it was noted that subendocardial hemorrhage occurs subsequent to brain death,50 and that EKG changes simulating myo-cardial ischemia occur in patients dying from intracranial hemorrhage, status epilepticus, meningoencephalitis, or traumatic brain herniation.51 Neuroendocrine changes consequent to anoxic brain death are marked by an initial hypertensive response due to catecholamine release, followed by progressive vasomotor tone collapse. Free triiodothyronine (T3), thyroxine (T4), cortisol, and insulin, TSH, and ADH decrease significantly within a few hours of the onset of brain death. Myocardial ATP, creatine phosphate, glycogen stores subsequently decrease and myocardial lactate increases. The rates of glucose, pyruvate, and...

Safety issues 1241 In animals

Fatty liver while the 9c,11t isomer had little or no effect (Clement et al., 2002 Degrace et al., 2003). While adipose tissue mass was shown to decrease after feeding CLA for 6 days, plasma levels of leptin and adiponectin decreased after 2 days of feeding, and hyperinsulinaemia developed on day 6 (Poirier et al., 2005). CLA was shown to alter the capacity of pancreatic islets to secrete insulin and the increase in insulin secretion was correlated to an increase in beta cell mass and number, leading to liver steatosis (Poirier et al., 2005). Degrace et al. (2003) demonstrated using C57BL 6J mice that the steatosis was not due to an alteration of the liver lipoprotein production. A three-fold decrease in plasma triacylglycerol and induction of mRNA expression of low-density lipoprotein receptors suggest an increase in the lipoprotein clearance at the level of liver. Further work also indicated that the steatosis was not due to impaired fatty acid oxidation as in fact in the liver,...

Overview of Defects in Thermogenesis in Rodent Models of Obesity

From the earliest studies of the obese mouse (now called leptin-deficient C57BL 6J Lepofe), there was evidence that these mice were not only obese, hyperglycemic, and hyperinsulinemic, but that they exhibited extreme sensitivity to the cold.10 Histologically, brown adipose tissue in these obese animals appears inactive in that it is infiltrated by white adipocytes and does not possess the rich density of mitochondria expressing UCP1 as normally seen in lean animals. The blunted capacity for adrenergic stimulation of lipolysis in adipose tissue of these animals (described below) probably also hinders the activation of UCP1 function by free fatty acids. Other monogenic obesity models and hypothalamic lesioning studies in rodents indicated a complex set of neural and endocrine abnormalities, culminating in the loss of homeo-static mechanisms controlling both food intake and metabolic efficiency.11 The suggestive role for brown fat and thermogenesis in body weight regulation was...

Identity of UCP Homologs and Genetic Linkage with Body Weight Disorders

Sporadic observations that the brown fat UCP could be detected (primarily when using antisera to measure protein levels) in other tissues such as mus-cle,19 led Ricquier and colleagues to search for homologues of the UCP. In 1997, Fleury et al.20 reported the cloning of UCP2. In addition to significant homology (59 ) with the brown fat UCP (now named UCP1) and the ability to uncouple respiration as efficiently as UCP1 in model systems, we found that UCP2 was broadly expressed in many tissues. This led to the hypothesis that UCP2 was the long-sought explanation for the relative inefficiency of oxidative respiration seen in most cell types. We also noted that the UCP2 gene resides in a chromosomal location on distal mouse chromosome 7 that is coincident with a quantitative trait locus (QTL) linkage to hyperinsuline-mia and high plasma leptin levels (reflective of body fat stores). In addition, we showed that the expression of UCP2 was specifically elevated in white adipose tissue in...

Adrenodoxin and Adrenodoxin Reductase

The PdR Pd system has a counterpart in the mammalian adrenal mitochondria, where the NADPH-dependent, FAD-containing adrenodoxin reductase (AdR) transfers electrons to the 2Fe-2S ferredoxin adrenodoxin (Adx), which in turn reduces mitochondrial P450 enzymes involved in steroidogenesis. Detailed studies have been done on the interactions between Adx and the mammalian CY-P11A1 and CYP11B enzymes, involved in cholesterol side-chain cleavage (the first step in the steroid synthesis pathway) and in formation of cortisol and aldosterone, respectively 37 . The AdR and P450 proteins are membrane-associated, but the Ad is a soluble protein. The nature of this type of P450 redox system (analogous to that seen for P450cam and other bacterial P450s, but markedly different from that supporting P450s in other mammalian tissues) is consistent with the endosymbiont theory of mitochondrial evolution.

Specific treatments for severe sepsisseptic shock

'Low-dose' hydrocortisone (50mg qds) given for 7 days improved outcomes if commenced within 8h of septic shock presentation, though only in the subset with an abnormal cortisol response to synthetic ACTH. Our current practice is to start hydrocortisone after performing a Synacthen test and to discontinue this therapy if the test is normal.

Child characteristics

However, autonomic arousal has shown a consistent, albeit modest, association with persistent antisocial behaviour in young people. Their pulse rates are lower, their skin conductance is less, as is their rate of adrenaline and cortisol excretion. Some have postulated that this leads to less anxiety when taking risks, (44) while others see it as part of a wider picture of decreased central nervous system inhibition. (45) With all these physiological substrates and mechanisms, the direction of effect is unlikely to be only biology-driven behaviour equally, confrontational situations, social dominance, peer rejection, and self-esteem do influence physiological parameters.

Aetiology of depression

Children with a high familial loading for major depression showed profiles of lower cortisol and higher prolactin levels following 5-hydroxy-L-tryptophan infusion similar to those of currently depressed children, both of which are significantly different from controls. (75 These early findings suggest that altered serotonergic regulation may precede first-episode early-onset depression in some cases. A loss of diurnal rhythm in selected adrenal steroids has also been noted in subjects at high risk for depression 51.) Both cortisol and dehydroepiandrosterone hypersecretion precede and predict the subsequent onset of major depression in high-risk subjects. (79 These abnormal steroid profiles are not a consequence of either current social adversities or negative cognitions or high emotionality. The associations between the genetic, social cognitive, and neurobiological factors prior to onset, during an episode, or following recovery are unknown.

Actions Of The Corticosteroids

The designation glucocorticoid activity is arbitrary, since naturally occurring glucocorticoids, such as cortisol, also possess mineralocorticoid activity, and the principal mineralocorticoid, aldosterone, when administered in very high doses, has glucocorticoid activity. Moreover, hydrocortisone, as well as certain synthetic glucocorticoids, such as prednisone and dexametha-sone, binds to mineralocorticoid receptors. However, the distinction between these two groups serves a useful purpose when dissociation of the basic actions becomes crucial for optimizing steroids' therapeutic efficiency.

Other Endocrine Organs

Since the synthesis and release of cortisol are regulated by pituitary corticotrophin, removal of the pituitary gland results in decreased function and eventual atrophy of the zona fasciculata and zona reticularis. Infusion of supraphysiological concentrations of cortisol will suppress corticotrophin secretion from the pituitary and will markedly decrease circulating corticotrophin levels. This occurrence implies a negative feedback control for corticotrophin and corticosteroid release (Fig. 60.3). In addition to the humoral control of corticotrophin release, direct nervous control is mediated through the median eminence of the hypothalamus (Fig. 60.3). Nerve terminals in the median eminence store and release various hormones and neurotransmitters, including corticotropin-releasing factor (CRF), which is under the control of higher neural centers. During stress, CRF is released into the pituitary portal system to stimulate corticotrophin release. Activation of the...

Congenital Adrenal Hyperplasia

Congenital enzymatic defects in the adrenal biosyn-thetic pathways lead to diminished cortisol and aldo-sterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hy-perplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90 of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is created by mutations in the CYP21 gene encoding the en

Characterization Of Plasma Androgens

Concentrations of plasma testosterone and other androgens vary throughout the day in both sexes whether such variation is simply random or fits a re-peatable diurnal pattern is a matter of debate. Compared with the diurnal variation seen with Cortisol, plasma testosterone concentrations are reasonably constant. Plasma androgen concentrations also vary greatly in women through the menstrual cycle, with peak levels seen in the luteal phase.

Clinical use of isoflurane in the ICU

Recovery from isoflurane sedation is very rapid, and procedures requiring disconnection from the ventilator, such as physiotherapy, may require administration of a supplementary agent such as morphine or alfentanil. There is no significant evidence for tolerance to the agent, although this has been reported in one child. There is no evidence that use of isoflurane impairs response to infection. Isoflurane reduces plasma catecholamine concentrations, but prolonged low-dose isoflurane does not inhibit cortisol production.

Immune Responses to Acute Psychological Stressors in MS

Several studies have examined acute responses to psychological stress in patients with relapsing forms of MS compared with healthy controls. Ackerman (Ackerman et al., 1996,1998), using a 5-min stressor based on the Trier Social Stress Test (TSST) (Kirschbaum et al., 1993), showed a good response to the stressor as marked by self-reported stress, heart rate, blood pressure, and plasma cortisol. Subjects also showed proliferation across a variety of immune cells and increased production of IL-10, TNF-a, and IFN-y after whole-blood stimulation with a nonspecific antigen. Although MS patients produced more IFN-y overall compared with controls, there were no differences between MS patients and healthy controls in the magnitude of the inflammatory response to stress.

Native Microorganisms in Steroid Biotransformation

Isms such as eubacteria, actinomycetes, fungi imperfecti, and more. In 1937, the development of technically useful microbial processes in steroid production began at Schering with the synthesis of testosterone. After the pharmacological effects of cortisol and progesterone became known, research in this field developed rapidly in the 1950s and led to the identification of a panel of different microorganisms that catalyze steroid hydroxylations, hydrogenations, dehydroge-nations, and the splitting of carbon-carbon bonds (reviewed in detail by 23 ). However, only a limited number of microbial transformations reported in the scientific literature have actually been applied technically. These comprise side-chain degradation reactions, A1,2-, A1,4-, 17P-dehydrogenation, and several hydroxylation reactions. Among the latter ones 11a-hydroxylation, 11P-hydroxyl-ation, and 16a-hydroxylation, are of the highest commercial significance and are therefore discussed in detail below.

Three Hypotheses Regarding the Mechanisms by Which Stress Leads to Exacerbation

Stressors occur over a period of time, particularly those such as family-or work-related, and stressors resulting from disruptions in routine. The biological mediators of stressors vary, depending on the point in the evolution of the stressor one examines. The onset of a stressor, particularly if the onset is sudden, salient, and intense, is often accompanied by sympathetic activation, increases in epinephrine and norepinephrine, and activation of the HPA axis. As the stressor becomes chronic, the HPA axis can become dys-regulated, often resulting in higher levels, and sometimes lower levels, of circulating cortisol (Sapolsky et al., 2000). Resolution or adaptation to the stressor under normal circumstances results in re-regulation of the HPA axis and return of circulating levels of cortisol to baseline. Thus, the neuroendocrine processes that mediate stress change with the evolution of the stressor.

Polymorphisms Affecting Drug Receptors And Targets

Polymorphisms affecting steroid hormone nuclear receptors may affect individual response to drugs and hormones. For example, glucocorticoid resistance in asthma patients has been associated with increased expression of the glucocorticoid receptor -isoform (Sousa et al., 2000) activating mutations of the mineralocorticoid receptor have been linked to hypertension exacerbated by pregnancy (Geller et al., 2000) and dominant negative mutations of peroxisome proliferator-activated receptor gamma (PPAR gamma) have been associated with severe insulin resistance, diabetes mellitus and hypertension (Barosso et al., 1999). Huizenga et al. (1998) identified a polymorphism affecting the glucocorticoid receptor that was present in 6 of their elderly study population. These individuals appeared healthy, but exhibited increased sensitivity (reflected in cortisol suppression and insulin response) to exogenously administered glucocorticoids. The authors postulated that this increased lifelong...

Stress Onset The Mast Cell Hypothesis

In our experience, many patients complain that the effects of stress on MS symptoms can occur within hours. We are not aware of any good empirical work in humans that confirm or disconfirm these reports. Laboratory stressors such as the Trier Social Stress Test (TSST) have been shown to produce significant elevations in proinflammatory cytokines in some studies (Ackerman et al., 1996,1998), although not in others (Heesen et al., 2002, 2005). (We note that Ackerman reported in a personal communication that the cognitive tasks are not as effective as public speaking in eliciting a neuroendocrine stress response among MS patients, possibly because MS patients do not expect themselves to perform as well on cognitive tasks the two studies that did not elicit a stress response only used cognitive tasks.) However, even when the TSST produced increases in proinflammatory cytokines, these elevations were similar to those seen in healthy controls. Similarly, acute stressors such as injury have...

Melatonin As A Marker For Circadian Phase Position

Cadian Rhythm

Determination of circadian phase, normal and pathological, can be done in a number of ways. The easiest but least reliable way is to use the timing of sleep (sleep offset is usually more reliable than sleep onset). Other physiological measures are more reliable but are sometimes difficult to assess, such as core body temperature and cortisol. There are also disagreements over how these data should be collected, specifically whether or not it is necessary or even desirable to use a constant routine in which semi-recumbent subjects are sleep deprived and fed isocalorically for one or two days (26-27).

Malnutrition syndromes of childhood

Infantile anorexia was first described in a series of case studies, and was initially thought to be a separation disorder 6 . These children exhibit extreme food refusal and frequently fail to take in sufficient calories to sustain growth, and as a result display acute and or chronic malnutrition. Eating disorders, such as bulimia (BN) and anorexia nervosa (AN), in childhood are characterized by a seriously undernourished state. In contrast, changes in the immune system have been less clear-cut and do not appear to follow the more typical types of malnutrition, such as PEM. In general, adaptive immunity seems to be preserved over long periods and susceptibility to viral infection is not common outside the advanced stages of disease. However, altered cell-mediated immunity in AN and BN is reflected in lymphocyte subset balance and poor response to delayed hypersensitivity tests 122 . A recent study compared healthy women to both underweight AN and normal-weight BN patients and reported...

Neurobiological mechanisms

Septohippocampal System

The hypothalamic-pituitary-adrenal axis and its end-product, cortisol, also are involved in reactions to stress. Activity in the hypothalamic-pituitary-adrenal axis is subject to a variety of influences. Primary control is by means of hypothalamic secretion of corticotrophin-releasing factor, which stimulates pituitary secretion of ACTH, which in turn stimulates adrenal secretion of cortisol. Circulating cortisol, and analogues such as dexamethasone, exert inhibitory feedback at the level of the pituitary gland and apparently also by means of receptors on the hippocampus. In rats, chronic exposure to stress or exogenous steroids results in a reduction of corticosteroid receptors in the hippocampus and a consequent decrease in feedback inhibition by cortisol.(33) These animals exhibit reduced dexamethasone suppression of cortisol secretion and greater or more prolonged adrenocortical responses to stress. Reduced dexamethasone suppression also has been observed in approximately...

Fattal Valevsk 2001 On Micronutrient

21 Dovio A, Caramello V, Masera RG, Sartori ML, Saba L, Tinivella M, Prolo P, Termine A, Avagnina P, Angeli A (2004) Natural killer cell activity and sensitivity to positive and negative modulation in uncomplicated obese subjects relationships to leptin and diet composition. Int J Obes Relat Metab Disord 28 894-901 23 Sanchez-Margalet V, Martin-Romero C, Santos-Alvarez J, Goberna R, Najib S, Gonzalez-Yanes C (2003) Role of leptin as an immunomodulator of blood mononuclear cells mechanisms of action. Clin Exp Immunol 133 11-19 24 Faggioni R, Feingold KR, Grunfeld C (2001) Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 15 2565-2571 25 Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S, Trussell RA (2004) Congenital leptin deficiency due to homozygosity for the Delta133G mutation report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab 89 4821-4826 Mancuso P, Gottschalk A,...

Microvascular Permeability in Preeclampsia

There is evidence that sera from women with pre-eclampsia rather that normal pregnancy increase the permeability of HUVEC monolayers. This suggests that there may be a factor or factors present in the maternal circulation that are responsible for the increased microvascular permeability in pregnancies complicated by the disease. Maternal circulating factors that are elevated in pre-eclampsia and may affect microvascular permeability include vascular endothe-lial growth factor (VEGF), angiopoietins, leptin, proinflammatory cytokines such as tumor necrosis factor-a (TNF-a), and, more recently, neurokinin B. The possible mechanism ) of action of these circulating factors on microvascular permeability are discussed next. Leptin Leptin, a protein product of the obesity gene, plays an important role in regulation of body weight in the nonpreg-nant state through its receptors in the satiety center of the hypothalamus. Endothelial cells also express leptin receptors. Their activation induces...

Introduction to lipoprotein metabolism

Non-esterified fatty acids are carried in the plasma bound to albumin. Some fat-soluble micronutrients and regulators of metabolism - e.g. fat-soluble vitamins and steroid hormones - are transported in the plasma by specific carrier proteins such as the cortisol-binding globulin, which carries cortisol. The transport of both triacylglycerol and cholesterol occurs in specialised macromolecular structures known as lipoproteins. Because triacylglycerol and cholesterol are carried by the same system, the metabolism of these two types of lipid in the plasma is closely interrelated.

Effecs Of Irr On Wound Healing

In addition to insulin, the adipocyte-derived hormones leptin and adiponectin are involved in fatty acid metabolism, as well as the recently identified acylation-stimulating protein (ASP). Leptin directly inhibits fatty acid synthesis4445 and increases the release and oxidation of fatty acids by activating hormone-sensitive lipase.46 Leptin also has multiple additional metabolic and endocrine functions. Leptin functions in immunoregulation, inflammation, and hematopoiesis,47 and regulates food intake by communicating with the hypothalamus about the degree of fat stores and changing eating behavior accordingly to maintain a level of homeostasis.48 It may also regulate TAG homeostasis by restricting TAG storage primarily to adipocytes and sparing nonadipocytes.49 Leptin deficiency may lead to hyperglycemia, hyperinsulinemia, and insulin resistance.50 A review of the role of leptin in lipid metabolism provides more information on this topic.51 A possible role for leptin in wound healing...

Immune dysfunction and malnutrition

Chemotaxis, phagocytosis, and microbial killing mechanisms are potentially impaired in malnutrition through reduced production of key mediators including complement C3, leukotrienes, cathelicidin antimicrobial peptide and leptin 33-36 . Children who are malnourished mount a partial acute phase response to infection and this defect is more marked in children with the edematous form 37 . The activities of innate immune cells such a neutrophils, monocytes, macrophages, and dendritic and NK cells are affected by altered nutrient levels 38-43 . These effects can be particularly critical in the perinatal period of immune development 44, 45 . Thymic atrophy caused by PCM is associated with hormonal imbalance, loss of leptin, and increase in serum glucocorticoid level. Leptin levels normally increase acutely during infection and inflammation 24 , but this does not occur in PCM. The reduction of serum leptin levels and insulinlike growth factor-1 (IGF-1) in marasmus and kwashiorkor 50 may...

The period of adaptation to starvation

Pylori And Species

Blood glucose concentrations fall very gradually in prolonged starvation and they are followed by the plasma insulin concentration. Glucagon concentrations, on the other hand, rise, so that the ratio of insulin glucagon reaching the liver must change considerably from early to late starvation. The plasma leptin concentration also falls. In longer starvation this may be due to a reduction in adipose tissue mass, but in the shorter term it also reflects a 'sensing' of energy deficit in adipose tissue, perhaps through reduced insulin concentrations (insulin will acutely stimulate leptin secretion from adipose tissue after feeding). The onset of starvation is also marked by a decrease in the level of the active thyroid hormone, triiodothyronine (T3, see Fig. 5.8), in the blood (Fig. 8.4). Several factors appear to cause this. The early reduction in secretion of thyroid hormones has been attributed to the fall in leptin action on the hypothalamus (reducing thyroid-stimulating hormone...

Neurohumoral responses in relation to hyperthermiainduced fatigue

Receptor blockade did not influence exercise performance, plasma prolactin or cortisol, and these parameters were also unchanged following administration of paroxetine, a selective 5-HT re-uptake inhibitor, which in addition failed to influence the core temperature response during exercise (Meeusen et al., 2001).

Introduction For Sleep Deprivation

IL-6 is a central neuroimmunological factor, and is one of the proinflammatory cytokines produced following immune challenges that contribute to stimulate the hypothalamic secretion of corticotropin releasing factor (CRF), the factor responsible for inducing secretion of adrenocorticotropin hormone (ACTH) by the anterior pituitary. ACTH regulates production and secretion of glucocorticoids by the adrenal cortex (i.e., cortisol in fish and Homo sapiens, corticosterone in rodents), which down-regulate both the HPA axis, and immune inflammatory events mediated by CMI. Autonomic neural activity, which includes palmar skin conductance, brachial artery systolic blood pressure, electrocardiogram, interbeat duration between R spikes, finger photoplethysmograph pulse peak amplitude, and peripheral finger photoplethysmograph peak during the final 60 s of a 15-min resting period, expressed as the SD of each indicator about its mean under each assessment condition, also plays a significant role...

Psychoneuroendocrinological research in personality disorders

Recent research has revealed the impact of social conditions on the neuroendocrine regulation of the individual, particularly with respect to the adaptation to stressful situations. In our sample of patients with a borderline personality disorder and impulsive suicidal behaviour we have found high basal concentrations of cortisol (suggesting a high level of stress) and a very blunted response to the stimulus (suggesting a reduced capacity to respond to external stimulus) compared with the control group. We have found the same pattern in heroin-dependent individuals receiving naltrexone maintenance treatment. A clue to the interpretation of these results lies in the work of Sapolsky, (45 who has studied the adaptation to stress of baboons in the Serengeti savannah in Africa. Males of a lower rank have consistently high concentrations of the stress hormone hydrocortisone in their blood, whereas the concentration is lower in the dominant males. However, in the dominant males...

Corticotropin deficiency

Pituitary corticotropin normally stimulates the adrenal cortex to secrete a cascade of steroids including cortisol, and its own secretion is principally stimulated by hypothalamic corticotropin-releasing hormone and arginine vasopressin ( ThorneLMM 1992). Cortisol exerts negative feedback inhibition at the basophil cell level. induces elevated serum cortisol concentrations with loss of circadian rhythm. This hypothalamic-pituitary-adrenal response to prolonged stress induced by trauma or sepsis was recently found to be biphasic. In the first phase, lasting for a few days, the high cortisol levels appear to be induced by augmented corticotropin release, which in turn is presumably driven by cytokines and the noradrenergic system. In the second phase, there is a discrepancy between low corticotropin and high cortisol levels, suggesting that cortisol release is stimulated through an alternative pathway. The hypercortisolism elicited by disease or trauma can be interpreted as an attempt...

Sleep Disturbances in Diseased States Associated with Altered Cytokine Profile

It was supposed that melancholic depression represents activation of the principal effectors of the stress resulting in higher NE and CRH levels. Centrally, NE acts as a major alarm-producing neurotransmitter in the brain that inhibits sleeping. It was shown, that depressed patients had significantly higher NE as well as plasma and cerebrospinal fluid (CSF) cortisol levels, while despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and that of CRH in their CSF (Wong et al. 2000 Leonard 2001b). Symptoms of depression can often be observed after treatment of patients with high doses of IFN-a or IL-2 (e.g., in chronic hepatitis or in malignant melanoma) (Capuron and Miller 2004). However, great differences exist in the prevalence of the development of depressive symptoms across studies. These symptoms include abnormal sleep patterns, irritability, anxiety, cognitive impairments, lethargy, and anorexia (Kronfol and Remick 2000 Corcos, Guilbaud, Hjalmarsson,...

The components of energy expenditure

The total expenditure of energy over a 24-hour period can be broken down into the basal metabolic rate, the energy cost of physical activity and diet-induced thermogenesis (Fig. 11.3). Physical activity varies considerably from person to person. However, the largest component of the 24-hour energy expenditure is, for most people, the basal component. The basal metabolic rate is very closely related to the amount of non-fat tissue in the body, the fat-free mass or lean body mass.2 The larger someone's fat free mass, the larger (in general) their basal metabolic rate (this will be illustrated later, in Fig. 11.5). The basal metabolic rate is also regulated by hormones, primarily by the thyroid hormone, triiodothyronine. During starvation or food deprivation thyroid hormone concentrations fall and basal metabolic rate decreases (see Section The significance of this for weight reduction programmes will be discussed again later. Leptin does not seem directly to regulate energy...

Carbohydrate type glycaemic response and weight control

Short- and long-term studies in humans and animals indicate that high-GI diets affect appetite and nutrient partitioning to promote fat storage. However, human studies showing reduced bodyweight after consumption of low-GI diets need to be interpreted with caution. The outcome can rarely be attributed solely to the GI, because interventions designed to modify the GI of a diet usually also modify other variables that influence bodyweight (e.g. fibre content, palatability, energy density). Pawlak et al. (2004) assigned rats and mice either to a low- or a high-GI diet. The carbohydrate portion of the low-GI diet consisted of 60 amylose 40 amylopectin starch, whereas the carbohydrate in the high-GI diet was 100 amylopectin starch. Other than this, the two diets were similar in nutrient and energy content. In both mice and rats, animals consuming the high-GI diet had more body fat and less lean body mass than those on the low-GI diet. The rats on the high-GI diet required less food to gain...

Neurological Disorders and Neurodegenerative Diseases

ACTH-dependent hypersecretion of glucocorticoids induces Cushing's syndrome. Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. The symptoms of Cushing's syndrome vary, but most people show upper body obesity, a rounded face, an increase in the neck region and thinning arms and legs. Children tend to be obese with slowed growth rates. Additional symptoms afflict the skin, which becomes fragile and thin. Most patients suffer from severe fatigue, weak muscles, high blood pressure and high blood sugar. Irritability, anxiety and depression are common. Cushing's syndrome can develop due to an overproduction of Cortisol, because of over-stimulation by ACTH.

The Il6 Response To Exercise

Finally, exercise-induced IL-6 production may also have an indirect role in mediating leukocyte trafficking of natural killer (NK) cells and neutrophils 90 . As described below, it appears that the acute exercise effect on NK cells is mediated by catecholamines, in particular epinephrine 42 . However, the post-exercise decline of NK cell activity and post-exercise neutrophi-lis is mediated by Cortisol. The latter hormone is of particular interest, if the exercise is of long duration. The increase in Cortisol is mediated by IL-6 91 . Linking exercise-induced changes in NK cells and neutrophils to an effect of IL-6 on Cortisol production, is further supported by several studies demonstrating that carbohydrate loading during exercise attenuates the exercise

Physiological factors influencing food intake

Long-term food intake regulation is essential in food-weight management. The hormone leptin appears to be involved in long-term food intake regulation. Leptin is synthesized mainly by adipose tissue it acts through receptors present in afferent visceral nerves and the hypothalamic arcuate Plasma leptin concentrations correlate positively with total body fat stores (Sinha et al., 1996). An energy deficit of more than 24 h leads to decreases of plasma leptin concentration (Boden et al., 1996), whereas an energy surplus of more than 24 h results in increased leptin concentrations (Kolaczynski et al., 1996). Plasma leptin is negatively correlated with appetite and food intake when the energy balance is severely disturbed (Keim et al., 1998 Chin-Chance et al., 2000). When subjects are in energy balance, the relation between leptin concentrations and food intake and appetite is less clear (Karhunen et al., 1997 Joannic et al., 1998 Romon et al., 1999). Therefore, leptin seems to have a role...

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