title: Androgen biosynthesis from cholesterol to DHEA.
abstract: Androgens and estrogens are made from dehydroepiandrosterone (DHEA), which is made from cholesterol via four steps. First, cholesterol enters the mitochondria with the assistance of the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia. Second, within the mitochondria, cholesterol is converted to pregnenolone by the cholesterol side chain cleavage enzyme, P450scc. Third, pregnenolone undergoes 17alpha-hydroxylation by microsomal P450c17. Finally, 17-OH pregnenolone is converted to DHEA by the 17,20 lyase activity of P450c17. The ratio of the 17,20 lyase to 17alpha-hydroxylase activity of P450c17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated post-translationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase, the presence of cytochrome b(5), and the serine phosphorylation of P450c17. Study of these and related factors may yield important information about the pathophysiology of adrenarche and the polycystic ovary syndrome (PCOS).
authors.affiliation: Department of Pediatrics, University of California, Bldg MR IV, Room 209, San Francisco 94142-0978, CA, USA. wlmlab@itsa.ucsf.edu
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000311:Adrenal Glands / Q000254:growth & development / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008064:Lipidoses / Q000235:genetics / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000728:Androgens; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D012694:Serine; D003687:Dehydroepiandrosterone; D002784:Cholesterol; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme