Steroidogenesis in dispersed cells of human fetal adrenal.
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.
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
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