The pituitary gland, about the size of a pea, is situated on the under-surface of the brain (Fig. 5.1), attached through a little stalk to the area of the brain known as the hypothalamus. The pituitary gland is also known as the hypophysis, or 'growth underneath'; removal of the pituitary gland is the operation called hy-pophysectomy. The hypothalamus, which itself lies under the thalamus, is the seat of integration of incoming signals from nerves with specialised 'sensing'
functions, and outgoing nervous activity, particularly in the sympathetic nervous system; it will be discussed in more detail in Section 18.104.22.168. The location of the pituitary gland in close proximity to the hypothalamus is no mere chance.
The pituitary gland has two major parts, or lobes: the anterior pituitary - also called the adenohypophysis - and the posterior pituitary, or neurohypophysis. The adenohypophysis contains cells which manufacture and secrete hormones. Regulation of the synthesis and secretion of its hormones is controlled, however, by other signals (local hormones) coming down a system of blood vessels in the stalk from the hypothalamus. The neurohypophysis is composed mainly of nerve cells that have their cell bodies in the hypothalamus. It is not a true endocrine organ; rather, the hormones which it releases are synthesised in the hypothalamus, transported along axons and stored temporarily before being secreted in response to nervous stimuli from the hypothalamus. Thus, the hypothalamus controls both nervous signals and hormonal signals to the rest of the body.
The hormones produced by the pituitary gland and their target organs are shown in Fig. 5.6.
5.3.1 Hormones of the anterior pituitary (adenohypophysis)
The anterior pituitary secretes at least six distinct peptide and glycoprotein hormones. Several act on other hormone-producing organs to influence the secretion of further hormones: they are known as tropic (or trophic) hormones. Of these, follicle-stimulating hormone (FSH) and luteinising hormone (LH) (known together as gonadotrophins) have functions in the reproductive system that will not be considered further.
Adrenocorticotrophic hormone (ACTH) - sometimes called cortico-trophin - is a peptide hormone (of 39 amino acids) which acts on the adrenal cortex to stimulate release of glucocorticoids, particularly cortisol. ACTH is (like insulin) synthesised as a prohormone, but in this case a very large one called pro-opiomelanocortin (often abbreviated POMC). POMC is cleaved proteolytically to generate several biologically active peptides including 0-endorphin and met-enkephalin (natural ligands of the receptors for cocaine, and involved in feelings of well-being, e.g. in response to exercise), a-, 0- and y-melanocyte-stimulating hormones (acting on melanocytes to influence pigmentation) and ACTH. (The melanocyte-stimulating hormones may also have a role in appetite regulation; see Box 11.1.)
ACTH is released in response to stress. It also has an important circadian rhythm (24-hour cycle); it is at its highest, as is cortisol secretion, in the morning at about the time of waking. There is feedback control of ACTH secretion: high levels of cortisol suppress ACTH secretion.
Thyroid-stimulating hormone (TSH) - sometimes called thyrotropin - acts on the thyroid gland to stimulate the production of thyroid hormones and to stimulate growth of the gland (discussed further below, Section 5.4). Again there is a feedback system, so that in thyroid deficiency, for example, TSH levels in blood are high; this is usually a clearer diagnostic test than direct measurement of thyroid hormone levels themselves.
Two more hormones secreted by the anterior pituitary act on other tissues that are not endocrine: prolactin and growth hormone. Prolactin stimulates milk production in the mammary gland and will not be considered further.
Growth hormone is a peptide hormone (of 190 amino acids in humans), sometimes called somatotropin because of its major role in regulating growth and development (somato- referring to the body). It does not do this directly. Growth hormone stimulates the production in the liver of other peptide hormones known as the insulin-like growth factors, IGF-1 and IGF-2, formerly known as the somatomedins since they mediate the effects of somatotropin. As their name implies, the insulin-like growth factors have structural similarities with insulin. They exert stimulatory effects on growth, whilst growth hormone has no direct effect. Even in adults, however, growth hormone is secreted. This occurs mainly overnight, in discrete bursts during sleep. It has some direct metabolic functions, although their importance in adults is not fully understood. The most important is probably a stimulation of fat mobilisation. This is not a rapid effect (unlike the effects of adrenaline or noradrenaline acting through the cAMP system - see Fig. 2.4.3). After a single injection of growth hormone, there is a stimulation of lipolysis after 2-3 hours. Growth hormone also has an effect on hepatic glucose production, probably involving stimulation of both gluconeogenesis and glycogenolysis. Again, this is probably not an effect of short-term importance. Adults who have had their pituitary gland removed surgically (usually because of a tumour) are usually not given growth hormone replacement, as it is expensive, and has not until recently been thought necessary. Recently, a number of trials of growth hormone replacement have shown that such treatment results in a loss of body fat and an increase in lean body mass, including muscle, reflecting a combination of the lipolytic and anabolic (growth-promoting) effects. It may also result in a feeling of well-being which is thought to reflect in part increased availability of fuels for physical work - i.e. non-esterified fatty acids and glucose in the plasma.
5.3.2 Hormones of the posterior pituitary (neurohypophysis)
The anterior pituitary secretes two structurally similar 9-amino acid peptide hormones, oxytocin (causing the uterus to contract) and vasopressin, also called antidiuretic hormone. The last name (ADH) suggests an obvious function in regulating urine production (more specifically, in regulating urine concentration), but the name vasopressin shows that this hormone also has a potent effect in constricting certain blood vessels. It may also, under certain conditions (particularly stress states), have a role in metabolic regulation; it has been suggested that vasopressin can stimulate glycogen breakdown in the liver. This is brought about by a change in the cytosolic Ca2+ concentration rather than through an increase in cAMP. An interesting relationship between the different effects of vasopressin may be seen. We have already seen that glyco-gen is stored with about three times its own weight of water; the liver glycogen store of about 100 g is accompanied by 300 g water. Mobilisation of glycogen therefore liberates water into the circulation. In a severe stress state brought about by loss of blood, for example, vasopressin might have multiple actions: further loss of water through the kidney is prevented by its antidiuretic action; extra water is mobilised along with glycogen; fuel (glucose) is provided for the organism to help deal with the stress (e.g. to provide energy to run away from an aggressor); and the vasoconstrictor action helps maintain blood pressure despite the loss of blood.
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