Dual regulation of 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and dehydroepiandrosterone sulfotransferase by adenosine 3’,5’-monophosphate and activators of protein kinase c in cultured human adrenocortical cells

Jan M. McAllister, Peter J. Hornsby

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Abstract

The relationship between cAMP and protein kinase C in the regulation of 3β-hydroxysteroid dehydrogenase (3βHSD), 17α-hydroxylase, and sulfotransferase was examined in human fetal adrenocortical cells under defined serum-free conditions in culture. Forskolin induced 3βHSD and 17α-hydroxylase in a dose-dependent manner, with maximal effects at 10 nU. 12-O-Tetradecanoyl phorbol 13-acetate (TPA) at 1 nM depressed the induction of 17α-hydroxylase activity by forskolin by more than 95% and increased the stimulation of 3/JHSD activity by forskolin by 4- to 5-fold. Increases were maximal at 48–72 h of incubation. Dehydroepiandrosterone sulfotransferase activity increased over 48 h when cells were transferred to serumfree defined medium. Addition of 10 nM forskolin stimulated sulfotransferase activity only when cells remained in 10% serum. TPA at 1 nM inhibited the increase in sulfotransferase activity. The concentration of TPA required for inhibition of forskolinstimulated 17α-hydroxylase and sulfotransferase activity was similar to that required for enhancement of forskolin-induced 3/8HSD activity, suggesting that comparable levels of C kinase activation are involved in these events. Angiotensin II, carbachol, epidermal growth factor, and fibroblast growth factor had actions similar to those of TPA on one or more of these enzyme activities. TPA also had similar actions on enzyme activities when they were stimulated by cAMP analogs rather than by forskolin. These studies suggest that adrenal steroid biosynthesis is under dual regulation by cAMP and protein kinase C. cAMP induces enzymes required for synthesis of 17αhydroxylated steroids, including the adrenal androgens. Activation of protein kinase C may play a complementary role by enhancing the induction of enzymes required for non-17α-hydroxylated steroid biosynthesis and inhibiting those involved in the synthesis of androgens.

Original languageEnglish (US)
Pages (from-to)2012-2018
Number of pages7
JournalEndocrinology
Volume122
Issue number5
DOIs
StatePublished - May 1 1988

All Science Journal Classification (ASJC) codes

  • Endocrinology

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