Intra-adrenal regulation of androgen synthesis.
The adrenal cortex encloses the neuroendocrine medulla and is itself subdivided into three distinct zones, each having a specific function and regulation. While the glomerulosa and the fasciculata control vital systems of mineral and energy supply, which are stringently regulated by higher control factors, the function of the reticularis is less clear, beyond supplying a pool of weak androgens, and consequently we do not understand its redundant regulation. The following questions need to be answered: 1. How is the formation of dehydroepiandrosterone (DHEA) and androstenedione differently regulated from glucocorticoid synthesis in normally functioning adrenals? 2. How might growth factors, which increase prepubertally, prime the adrenarche? 3. The regulation of the 17/20-lyase enzyme activity is one of the key factors of adrenal androgen secretion (review [2]). How can the two activities of the P450c17 enzyme be differently regulated in the same cell in a developmentally dependent fashion? This review focuses on the intra-adrenal growth factor system and on the role of 17/20-lyase regulation, as well as on their possible interactions. The increase of activity of the 17/20-lyase enzymatic activity is necessary for the rise of C19 steroids, while the relative increase of formation of DHEA is only possible in the presence of a low 3beta-hydroxysteroid-dehydrogenase (3betaHSD) activity.
Department of Paediatrics, Humboldt University, Berlin, Germany.
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l'Allemand
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Biason-Lauber
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism / Q000502:physiology
D000728:Androgens; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase