Department of Histology and Embryology, Akdeniz University Faculty of Medicine, Antalya 07070, Turkey.
J Ovarian Res. 2012 Nov 27;5(1):38. doi: 10.1186/1757-2215-5-38.
Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder affecting 5-10% of women in reproductive age that is characterized by hyperandrogenism, oligo- or anovulation and infertility. However the pathophysiology of PCOS still remains unknown. The mammalian target of rapamycin (mTOR) is a central component that regulates various processes including cell growth, proliferation, metabolism, and angiogenesis. mTOR signaling cascade has recently been examined in ovarian follicles where it regulates granulosa cell proliferation and differentiation. mTOR functions as two complexes, mTOR complex 1 and 2. Therefore, we hypothesized that mTORC1 and/or 2 may have important role in proliferation of theca and granulosa cells in PCOS. In the present study, we sought to determine the mTOR signaling pathway in PCOS mouse ovary. We designed 3 groups: Control (C, no treatment), PCOS (P, The injection of DHEA (6 mg/100 g BW in 0.1 ml of sesame oil) (s.c) for 20 consecutive days), Vehicle (V, daily (s.c) sesame oil alone injection). Our results showed that mTORC1 and mTORC2-mediated signaling may play a role in PCOS mouse ovary. These findings provide evidence that mTORC1 and mTORC2 may have responsibility in increased ovarian follicular cell proliferation and growth in PCOS. Consequently, these results suggest that the mTOR signaling pathways (mTORC1 and mTORC 2) may create new clinical strategies to optimize developmental competence of PCOS should target correction of the entire follicle growth, oocyte development process and anovulatory infertility in PCOS.
多囊卵巢综合征(PCOS)是一种常见且复杂的内分泌疾病,影响着 5-10%的育龄妇女,其特征是高雄激素血症、排卵障碍和不孕。然而,PCOS 的病理生理学仍然未知。哺乳动物雷帕霉素靶蛋白(mTOR)是一种调节细胞生长、增殖、代谢和血管生成等多种过程的核心组成部分。mTOR 信号级联在卵巢卵泡中最近被研究过,它调节颗粒细胞的增殖和分化。mTOR 作为两个复合物发挥作用,即 mTOR 复合物 1 和 2。因此,我们假设 mTORC1 和/或 mTORC2 可能在 PCOS 的颗粒细胞和膜细胞增殖中发挥重要作用。在本研究中,我们试图确定 PCOS 小鼠卵巢中的 mTOR 信号通路。我们设计了 3 组:对照组(C,无处理)、PCOS 组(P,连续 20 天皮下注射 DHEA(6mg/100gBW 在 0.1ml 芝麻油中))和 Vehicle 组(V,每天皮下注射芝麻油)。我们的结果表明,mTORC1 和 mTORC2 介导的信号可能在 PCOS 小鼠卵巢中发挥作用。这些发现提供了证据表明,mTORC1 和 mTORC2 可能对 PCOS 中卵巢卵泡细胞增殖和生长增加负责。因此,这些结果表明,mTOR 信号通路(mTORC1 和 mTORC2)可能为优化 PCOS 的发育能力提供新的临床策略,应该针对整个卵泡生长、卵母细胞发育过程和 PCOS 的排卵障碍性不孕进行校正。