title: Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome.
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.
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism; D000367:Age Factors; D000446:Aldehyde-Lyases / Q000378:metabolism*; D000596:Amino Acids / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D005333:Fetus; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000209:etiology / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D010750:Phosphoproteins; D012694:Serine; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases; D000446:Aldehyde-Lyases