Steroidogenesis in Dispersed Cells of Human Fetal Adrenal*

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Abstract
Steroidogenesis in dispersed fetal zone cells of midtrimester human fetal adrenal was stimulated acutely by ACTH. Polypeptide hormones such as hCG, αMSH, 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 17α-hydroxypregnenolone. Only minimal production of the δ4-3-ketosteroids, cortisol, corticosterone, and progesterone, was observed. Cyanoketone (2α-cyano-4,4,17α-trimethyl-17β-hydroxyandrost-5-en-3-one; an inhibitor of 3β-hydroxysteroid dehydrogenase activity) treatment of the cells caused only a minor increase in 3β-hydroxysteroid formation, confirming that 3β-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 17α-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. (J Clin Endocrinol Metab56: 1057, 1983)