title: Human proopiomelanocortin-(79-96), a proposed androgen stimulatory hormone, does not affect steroidogenesis in cultured human fetal adrenal cells.
abstract: Whether the production of human adrenal androgens is stimulated by a hormone other than ACTH or angiotensin-II has long been controversial. A candidate for such a cortical androgen stimulatory hormone (CASH) is the proximal 18-amino acid hinge region of proopiomelanocortin (POMC). This region of POMC lies to the amino-terminal side of the ACTH region, displays considerable amino acid sequence variation among mammals, and has been reported to stimulate the secretion of dehydroepiandrosterone (DHEA) from cultured adult adrenal cells. We cultured human fetal adrenal cells with 10(-8) M CASH-18, 10(-13) M ACTH, 10(-8) M CASH-18 plus 10(-13) M ACTH, 10(-8) M ACTH, or vehicle alone. Culture media were assayed for cortisol, DHEA, and DHEA sulfate, and cellular RNA was assayed for P450scc and P450c17 mRNAs. ACTH (10(-8 M) increased steroid secretion and the mRNAs for P450scc and P450c17, but the other treatments were indistinguishable from the control. Thus, CASH-18 does not affect steroidogenesis in primary cultures of human fetal adrenal cells. These data could be consistent with a model in which adrenarche, the onset of adrenal androgen synthesis at 8-10 yr of age, is mediated by developmentally programmed synthesis of a receptor for CASH. Alternatively, they are also consistent with this region of POMC having no CASH activity.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143.
authors.forename: S H
authors.initials: SH
authors.lastname: Mellon
authors.forename: J E
authors.initials: JE
authors.lastname: Shively
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000595:Amino Acid Sequence; D000728:Androgens / Q000096:biosynthesis*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D000728:Androgens; D010446:Peptide Fragments; D012333:RNA, Messenger; C028182:proopiocortin fragments; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone