EFFECTS OF INSULIN AND IGFS ON OVARIAN STEROIDOGENESIS

育龄妇女的高雄激素血症是一种常见的临床症状。 有问题。对于绝大多数高雄激素女性来说，没有特定的 病因是可以确定的。这些病例通常被诊断为 患有“多囊卵巢综合征”。一个独特的机会来确定 多囊卵巢综合征的特定分子病因由 高胰岛素血症常见的临床观察 与高雄激素血症有关。这项研究提案的目的是 是为了研究胰岛素和胰岛素样生长因子的作用 (IGFS)对卵巢类固醇激素生成的影响。尤其是胰岛素的作用 和IGFS对小鼠卵泡膜和间质中雄激素产生的影响 将对卵巢进行详细检查。 我们实验室的初步发现支持这一假设 胰岛素刺激性腺雄激素的产生包括：1) 胰岛素刺激双氢睾酮、睾酮和雄烯二酮 在长期孵育中产生黄体酮，但不产生黄体酮 猪碎卵膜；2)胰岛素刺激睾酮代谢 对长期孵化的人卵泡膜和卵泡膜中双氢睾酮的影响 气孔；3)卵巢碎的孵化 人绒毛膜促性腺激素治疗瘦(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。 制作。 胰岛素对卵巢雄激素产生的影响将进一步 具有以下经验的：1)物种的测定 胰岛素对卵巢雄激素产生作用的特异性；2) 测定对阿司匹林的影响最敏感的卵巢间隔 胰岛素(膜细胞、气孔细胞或颗粒细胞)；3)分析 胰岛素样生长因子(IGF-I、IGF-II、松弛素)对卵巢的影响 雄激素合成；4)胰岛素结合特性分析 和IGF对卵巢膜和间质中存在的胰岛素受体的作用；5) 胰岛素和胰岛素样生长因子对卵泡膜特异性酶影响的分析 雄激素生物合成(5α-还原酶，17β-羟基类固醇 脱氢酶、17α-羟基酶和3β-羟基类固醇 脱氢酶)；以及6)卵巢的可能联系的研究 胰岛素受体是一种酪氨酸特异的蛋白激酶。

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.