Poretsky L, Kalin M F
Endocr Rev. 1987 May;8(2):132-41. doi: 10.1210/edrv-8-2-132.
We have reviewed the role of insulin in ovarian physiology. Clinical observations and experimental data strongly support the hypothesis that insulin possesses gonadotropic activity, when acting alone or with FSH or LH. This idea is further supported by the recent discovery of insulin in follicular fluid. The idea that insulin has gonadotropic function can explain a variety of clinical observations, which otherwise are difficult to understand. For example, manifestations of ovarian hypofunction (primary amenorrhea, late menarche, anovulation, low pregnancy rate, and early menopause) in IDDM can be understood if it is accepted that insulin is necessary for the ovary to reach its full steroidogenic potential. The idea that insulin affects ovarian steroidogenesis also helps to understand the observation that hyperandrogenism frequently accompanies each of the various insulin-resistant states, regardless of the latter's etiology (e.g. genetic deficiency in the number of insulin receptors, antiinsulin receptor antibodies, obesity, etc.). The explanation for this association is based on the idea that hyperinsulinemia intensifies ovarian steroidogenesis, which manifests clinically as hyperandrogenism. Continuous stimulation of the ovary by insulin over a long period of time possibly produces morphological ovarian changes, such as hyperthecosis or polycystic changes; these changes commonly are observed among women with insulin resistance. The effects of insulin on ovarian cells are mediated possibly through binding of the peptide to its own receptor or to the IGF-1 receptor (the specificity spillover phenomenon). The latter could be an important mechanism in cases of insulin resistance. Potential mechanisms underlying the gonadotropic activity of insulin include direct effects on steroidogenic enzymes, modulation of FSH or LH receptor number, synergism with FSH or LH, or nonspecific enhancement of cell viability. The gonadotropic function of insulin adds yet another note to what has been termed a symphony of insulin action. Further investigation into this new area may yield greater insights not only into normal ovarian physiology, but also into the pathogeneses of such diverse entities as PCO, obesity, diabetes mellitus, and the syndromes of insulin resistance and acanthosis nigricans.
我们回顾了胰岛素在卵巢生理中的作用。临床观察和实验数据有力地支持了这样一种假说：胰岛素单独作用或与促卵泡激素（FSH）或促黄体生成素（LH）共同作用时，具有促性腺活性。卵泡液中胰岛素的最新发现进一步支持了这一观点。胰岛素具有促性腺功能这一观点可以解释多种临床观察结果，否则这些结果很难理解。例如，如果认为胰岛素是卵巢发挥其全部类固醇生成潜能所必需的，那么胰岛素依赖型糖尿病（IDDM）中卵巢功能减退的表现（原发性闭经、初潮延迟、无排卵、低妊娠率和早绝经）就可以得到解释。胰岛素影响卵巢类固醇生成的观点也有助于理解这样一个观察结果：无论各种胰岛素抵抗状态的病因是什么（例如胰岛素受体数量的遗传缺陷、抗胰岛素受体抗体、肥胖等），高雄激素血症都经常伴随出现。这种关联的解释基于高胰岛素血症会增强卵巢类固醇生成这一观点，临床上表现为高雄激素血症。胰岛素长期持续刺激卵巢可能会导致卵巢形态学改变，如卵泡膜细胞增生或多囊性改变；这些改变在胰岛素抵抗的女性中很常见。胰岛素对卵巢细胞的作用可能是通过该肽与自身受体或胰岛素样生长因子-1（IGF-1）受体结合介导的（特异性溢出现象）。在胰岛素抵抗的情况下，后者可能是一个重要机制。胰岛素促性腺活性的潜在机制包括对类固醇生成酶的直接作用、FSH或LH受体数量的调节、与FSH或LH的协同作用，或对细胞活力的非特异性增强。胰岛素的促性腺功能为所谓的胰岛素作用交响曲增添了新乐章。对这一新领域的进一步研究不仅可能会让我们对正常卵巢生理有更深入的了解，还可能会让我们对多囊卵巢综合征（PCO）、肥胖、糖尿病以及胰岛素抵抗和黑棘皮病综合征等多种不同疾病的发病机制有更深入的认识。
