Zhang L H, Rodriguez H, Ohno S, Miller W L
Department of Pediatrics, University of California, San Francisco 94143-0978, USA.
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10619-23. doi: 10.1073/pnas.92.23.10619.
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.
微粒体细胞色素P450c17在同一活性位点催化类固醇17α-羟化酶活性以及C17-C20类固醇键的断裂（17,20-裂解酶）。整个生命过程中产生皮质醇都需要肾上腺17α-羟化酶活性，但17,20-裂解酶活性似乎以一种复杂的、年龄依赖性模式独立控制。我们发现人P450c17被一种cAMP依赖性蛋白激酶在丝氨酸和苏氨酸残基上磷酸化。P450c17的磷酸化增加17,20-裂解酶活性，而去磷酸化实际上消除了这种活性。人P450c17的激素调节丝氨酸磷酸化提示了人类肾上腺初现的一种可能机制，并且可能是多囊卵巢综合征所特有的高雄激素血症和胰岛素抵抗之间的一个统一病因联系。
