EFFECTS OF INSULIN AND IGFS ON OVARIAN STEROIDOGENESIS

育龄妇女高雄激素血症是一种常见的临床 问题. 对于绝大多数高雄激素女性来说， 可以确定病因。 这些病例通常被诊断为 患有“多囊卵巢综合症”。 一个独特的机会，以确定一个 多囊卵巢综合征的病因有哪些 近年来临床观察发现，高胰岛素血症 与高雄激素血症有关 本研究计划的目的 是研究胰岛素和胰岛素样生长因子 （IGFs）对卵巢类固醇生成的影响。 尤其是胰岛素的作用 和IGFs对卵泡膜和间质中雄激素产生的影响 将详细检查卵巢。 我们实验室的初步发现支持了这一假设， 胰岛素刺激性腺雄激素产生包括以下内容：1） 胰岛素刺激的双氢睾酮、睾酮和雄烯二酮 生产，但不是孕酮的生产在长期孵育， 猪卵泡膜碎; 2）胰岛素刺激睾酮代谢 在切碎的人卵泡膜的长期孵育中， 气孔;和3）孵化切碎的卵巢， 人绒毛膜促性腺激素hCG处理的瘦（ob/+或+/+）小鼠。 这些 结果表明，胰岛素可能是性腺雄激素的主要调节因子 生产 胰岛素对卵巢雄激素产生的影响将进一步研究 其特征在于以下实验：1）物种的确定 胰岛素对卵巢雄激素产生作用的特异性; 2） 确定对以下影响最敏感的卵巢隔室： 胰岛素（卵泡膜、气孔或颗粒细胞）; 3）分析 胰岛素样生长因子（IGFs）（IGF-I，IGF-II，松弛素）对卵巢 雄激素合成; 4）胰岛素结合特性分析 和胰岛素样生长因子对卵巢卵泡膜和间质中存在的胰岛素受体; 5） 胰岛素和胰岛素样生长因子对卵泡膜特异性酶活性的影响 雄激素生物合成（5 α-还原酶，17 β-羟基类固醇 脱氢酶、17 α-羟化酶和3 β-羟基类固醇 脱氢酶）;和6）调查卵巢癌的可能联系， 胰岛素受体与酪氨酸特异性蛋白激酶结合。

Hyperandrogenism in women of reproductive age is a common clinical problem. For the vast majority of hyperandrogenic women no specific etiologic cause can be identified. These cases are often diagnosed as having the "polycystic ovary syndrome". A unique opportunity to identify a specific molecular cause of the polycystic ovary syndrome is provided by the recent clinical observation that hyperinsulinemia is commonly associated with hyperandrogenism. The objective of this research proposal is to investigate the effects of insulin and insulin-like growth factors (IGFs) on ovarian steroidogenesis. In particular, the effects of insulin and IGFs on androgen production in the thecal and stromal compartments of the ovary will be examined in detail. Preliminary findings from our laboraroty which support the hypothesis that insulin stimulates gonadal androgen production include the following: 1) insulin stimulated dihydrotestosterone, testosterone, and androstenedione production, but not progesterone production in long-term incubations of minced porcine theca; 2) insulin stimulated the metabolism of testosterone to dihydrotestosterone in long-term incubations of minced human theca and stoma; and 3) incubations of minced ovaries from human-chorionic-gonadotropin hCG-treated lean (ob/+ or +/+) mice. These results suggest that insulin may be a major regulator of gonadal androgen production. The effects of insulin on ovarian androgen production will be further characterized by the following experients: 1) determination of the species specificity of the insulin effect on ovarian androgen production; 2) determination of the ovarian compartment most sensitive to the effects of insulin (theca, stoma or granulosa cells); 3) analysis of the effects of insulin-like growth factors (IGFs) (IGF-I, IGF-II, relaxin) on ovarian androgen synthesis; 4) analysis of the binding characteristics of insulin and IGFs to the insulin receptor present in ovarian theca and stroma; 5) analysis of the effects of insulin and IGFs on specific enzymes of thecal androgen biosynthesis (5alpha-reductase, 17Beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase, and 3Beta-hydroxysteroid dehydrogenase); and 6) investigation of the possible linkage of the ovarian insulin receptor to a tyrosine-specific protein kinase.