Corticosterone

Pathways of neurosteroid hormone synthesis in the central and peripheral nervous systems. The presence of most the enzymes listed have been identified at the enzymatic, protein, and mRNA levels. Transcription of the P450scc gene is regulated by tropic hormones adrenocorticotropic hormone (ACTH) in the adrenal, gonadotropins in the testes and ovaries, and by an unknown factor in the placenta, all working through cAMP as second messenger. In the brain, the P450scc gene is also...

Steroidogenic Cytochromes P450

Most steroidogenic enzymes are members of the cytochrome P450 group of oxidases (1,2). All of these enzymes have molecular weights about 50 kDa and contain a single heme group. They are called P450 (pigment 450) because they all exhibit a characteristic absorbance at 450 nm upon reduction with carbon monoxide (3). The mechanism by which all the steroidogenic P450s function is identical. They all reduce atmospheric oxygen with electrons from nicotinamide-adenine-dinucleotide phosphate (NADPH)....

The Role Of Guanine Nucleotide Proteins

Guanine nucleotide proteins (G-proteins) appear to regulate many cellular processes, ion channels and neurotransmitter release (20). Several neurotransmitters and several presynaptic receptors are known to modulate voltage-dependent Ca2+ channels, through surface receptors coupled to the Ca2+ channel via a G-protein-dependent mechanism (20). The actions of certain neuroactive steroids on their respective Ca2+ channel current appear to involve signal transduction pathway(s). The actions of the...

Neuroactive Steroids In Alcohol Dependence And Withdrawal

Neurosteroids that potentiate GABAA-receptor activity have characteristic behavioral effects resembling those of ethanol in many respects, including anxiolytic, anticonvulsant, and sedative-hypnotic activity (22-25). The neurosteroids of greatest current interest in alcohol research are allopregnanolone and its 21-hydroxy analog allotetra-hydrodeoxycorticosterone (3a,5a-THDOC). Allopregnanolone and 3a,5a-THDOC increase responding in the conflict portion of the Geller-Seifter test (anticonflict...

References

Wetterberg L. Steroid Hormone Regulation of the Brain, Pergamon, Oxford, UK, 1981. 2. McEwen BS. Steroid hormones are multifunctional messengers to the brain. Trends Endocrinol Metab 1991 2 62-67. 3. Naftolin F, Ryan KJ, Davies IJ, Reddy VV, Flores F, Petro Z, Kuhn M, White RJ, Takaoka Y, Wolin L. The transformation of estrogens by central neuroendocrine tissues. Recent Progr Horm Res 1975 31 295-319. 4. Celotti F, Melcangi RC, Martini LJ. The 5a-reductase in the...

Neurosteroids and Personality Aggressivity and Drug Dependence

Neuromodulatory actions of steroids at the GABAa receptors invite the speculation that their profile in plasma and the CNS contributes to different personality traits. The steroid profile is genetically determined it changes during the development, aging, preg nancy, stress, and in some pathologies. Theoretically, a higher proportion of excitatory steroids to inhibitory ones would result in anxiety-prone, introvert type of personality, characterized by higher level of resting arousal, greater...

About The Editors

Etienne-Emile Baulieu is Professor of Biochemistry and Professor of Human Reproduction at the Coll ge de France in Paris. He is also Research Director of the Unit on Steroid Hormones and Hormonal Communications at the National Institute of Health and Medical Research (INSERM). He is a cofounder of the World Health Organization (WHO) Program on Human Reproduction and a member of the French Acad mie des Sciences, National Academy of Sciences of the USA, and the Academia Europea. He is also a...

Enzymes Of Neurosteroid Biosynthesis In The Rodent Brain

Neurosteroids

Current View of Neurosteroid Biosynthesis The definition stricto sensu of neurosteroids applies to PREG, DHEA, and their sulfate and fatty acid esters and to PROG and its 5a-reduced metabolites (5a-DH PROG, 3a,5a-TH PROG, and 3p,5a-TH PROG). It is not our purpose to provide a detailed description of the biosynthetic and metabolic enzymes, as they are accounted for extensively in other chapters of this book (refs. 19,20, and 53) We mainly wish to provide a critical appraisal of present...