Serine Phosphorylation of Human P450c17 Increases 17,20-lyase Activity: Implications for Adrenarche and the Polycystic Ovary Syndrome

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Nov 7

PMID 7479852

Citations 85

Authors

L H Zhang

H Rodriguez

S Ohno

W L Miller

Affiliations

Soon will be listed here.

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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