title: Steroidogenesis in dispersed cells of human fetal adrenal.
abstract: Steroidogenesis in dispersed fetal zone cells of midtrimester human fetal adrenal was stimulated acutely by ACTH. Polypeptide hormones such as hCG, alpha MSH, ovine PRL, and LH did not produce a similar stimulation of steroidogenesis. The principal steroid products of ACTH-stimulated fetal adrenal cells were dehydroisoandrosterone sulfate, pregnenolone, pregnenolone sulfate, and 17 alpha-hydroxypregnenolone. Only minimal production of the delta 4-3-ketosteroids, cortisol, corticosterone, and progesterone, was observed. Cyanoketone (2 alpha-cyano-4,4,17 alpha-trimethyl-17 beta-hydroxyandrost-5-en-3-one; an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity) treatment of the cells caused only a minor increase in 3 beta-hydroxysteroid formation, confirming that 3 beta-hydroxysteroid formation is the principal steroidogenic fate of cholesterol in these cells. SU-10603 [7-chloro-3,4-dihydro-2-(3-pyridyl)naphthalen-1-(2H)one; a steroid 17 alpha-hydroxylase inhibitor] treatment of the cells caused a marked accumulation of pregnenolone sulfate, indicating that the C-19 steroids are produced from C-21 steroids in this tissue and possibly that dehydroisoandrosterone sulfate is synthesized directly from pregnenolone sulfate. ACTH-stimulated pregnenolone synthesis was inhibited by AY-9944 [trans-1,4-bis-(2-chlorobenzylaminomethyl) cyclohexane dihydrochloride; an inhibitor of cholesterol biosynthesis]. Thus, cholesterol synthesized de novo was the likely steroidogenic precursor in the acute hormonally stimulated fetal adrenal cells.
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000096:biosynthesis; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D003489:Cyanoketone / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate; D006801:Humans; D010907:Pituitary Hormones / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D010907:Pituitary Hormones; D013764:Tetrahydronaphthalenes; C018370:pregnenolone sulfate; D006907:17-alpha-Hydroxypregnenolone; D003489:Cyanoketone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; C001953:SU 10603; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase