Auchus R J, Geller D H, Lee T C, Miller W L
Department of Pediatrics, Bldg MR-IV Room 209, University of California San Francisco, San Francisco, CA 94143-0978, USA.
Trends Endocrinol Metab. 1998 Feb;9(2):47-50. doi: 10.1016/s1043-2760(98)00016-2.
The polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance, but the connection between these two features has been unclear. Androgen synthesis is regulated in part by the ratio of the 17alpha-hydroxylase and 17,20 lyase activities of P450c17. Three separate lines of evidence show that the ratio of lyase to hydroxylase activity is regulated by electron flow from P450 oxidoreductase. Lyase activity and androgen synthesis are particularly dependent on the serine phosphorylation of P450c17. Serine phosphorylation of the insulin receptor beta chain causes insulin resistance, and some PCOS women have hyperphosphorylated receptors. We hypothesize that an overactive serine/threonine kinase hyperphosphorylates both the insulin receptor and P450c17 in PCOS, accounting for the characteristic insulin resistance and hyperandrogenism of this disease.
多囊卵巢综合征（PCOS）的特征是雄激素过多和胰岛素抵抗，但这两个特征之间的联系尚不清楚。雄激素的合成部分受P450c17的17α-羟化酶和17,20裂解酶活性比值的调节。三条独立的证据表明，裂解酶与羟化酶活性的比值受来自P450氧化还原酶的电子流调节。裂解酶活性和雄激素合成特别依赖于P450c17的丝氨酸磷酸化。胰岛素受体β链的丝氨酸磷酸化会导致胰岛素抵抗，一些PCOS女性的受体存在过度磷酸化。我们假设，一种过度活跃的丝氨酸/苏氨酸激酶会使PCOS中的胰岛素受体和P450c17都过度磷酸化，这解释了该疾病的特征性胰岛素抵抗和雄激素过多。
