Kwintkiewicz Jakub, Giudice Linda C
Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, California 94143-0132, USA.
Semin Reprod Med. 2009 Jan;27(1):43-51. doi: 10.1055/s-0028-1108009. Epub 2009 Feb 5.
Over the past 20 years, the expression, signaling mechanisms, and roles of members of the insulin-like growth factor (IGF) family (ligands, receptors, binding proteins, and binding protein proteases and their inhibitors) have been elucidated in ovarian follicle function in humans and other species. In vitro studies with human, nonhuman primate, and farm animal granulosa and thecal cells and genetic approaches using mouse knockout models for IGF family members have revealed that IGFs are key intraovarian regulators of follicle growth, selection, atresia, cellular differentiation, and steroidogenesis, oocyte maturation, and cumulus expansion. Some of these actions are synergistic with gonadotropins, although most are not sustainable with IGFs alone and require gonadotropin actions, thereby designating IGFs as "co-gonadotropins." In the human disorder of polycystic ovarian syndrome, characterized by small antral follicle arrest, the IGF system appears to contribute to the observed resistance to follicle-stimulating hormone action at the level of the granulosa compartment and the persistence of an androgen-dominant milieu in the arrested follicles. Interestingly, recent studies demonstrate that endocrine-disrupting chemicals can compromise IGF activity and signaling in the ovarian follicle, affecting follicle development, steroidogenesis, and oocyte quality. The successful development of a healthy oocyte and appropriate granulosa and theca cell steroidogenesis on a cyclic basis are contingent on multiple factors, including a properly functioning intraovarian IGF system. Disruption of even one component of this system can lead to abnormal follicular development and function and compromised reproductive capacity.
在过去20年中，胰岛素样生长因子（IGF）家族成员（配体、受体、结合蛋白、结合蛋白蛋白酶及其抑制剂）的表达、信号传导机制和作用已在人类和其他物种的卵巢卵泡功能中得到阐明。对人类、非人灵长类动物和家畜颗粒细胞与卵泡膜细胞进行的体外研究，以及使用IGF家族成员的小鼠基因敲除模型的遗传学方法表明，IGF是卵泡生长、选择、闭锁、细胞分化、类固醇生成、卵母细胞成熟和卵丘扩展的关键卵巢内调节因子。其中一些作用与促性腺激素协同，尽管大多数仅靠IGF无法维持，需要促性腺激素的作用，因此将IGF称为“协同促性腺激素”。在以小窦状卵泡停滞为特征的人类多囊卵巢综合征疾病中，IGF系统似乎在颗粒细胞区室水平上导致了观察到的对促卵泡激素作用的抵抗，以及停滞卵泡中雄激素主导环境的持续存在。有趣的是，最近的研究表明，内分泌干扰化学物质会损害卵巢卵泡中的IGF活性和信号传导，影响卵泡发育、类固醇生成和卵母细胞质量。健康卵母细胞的成功发育以及颗粒细胞和卵泡膜细胞周期性地进行适当的类固醇生成取决于多种因素，包括正常运作的卵巢内IGF系统。该系统中即使一个成分受到破坏，也会导致卵泡发育和功能异常以及生殖能力受损。
