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Journal List > Proc Natl Acad Sci U S A > v.92(23); Nov 7, 1995

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Proc Natl Acad Sci U S A. 1995 November 7; 92(23): 10619–10623.
PMCID: PMC40663
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Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome.
L H Zhang, H Rodriguez, S Ohno, and W L Miller
Department of Pediatrics, University of California, San Francisco 94143-0978, USA.
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Abstract
Microsomal cytochrome P450c17 catalyzes both steroid 17 alpha-hydroxylase activity and scission of the C17-C20 steroid bond (17,20-lyase) on the same active site. Adrenal 17 alpha-hydroxylase activity is needed to produce cortisol throughout life, but 17,20-lyase activity appears to be controlled independently in a complex, age-dependent pattern. We show that human P450c17 is phosphorylated on serine and threonine residues by a cAMP-dependent protein kinase. Phosphorylation of P450c17 increases 17,20-lyase activity, while dephosphorylation virtually eliminates this activity. Hormonally regulated serine phosphorylation of human P450c17 suggests a possible mechanism for human adrenarche and may be a unifying etiologic link between the hyperandrogenism and insulin resistance that characterize the polycystic ovary syndrome.
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Selected References
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