Palumbo Angela, Ávila Julio, Naftolin Frederick
Centro de Asistencia a la Reproducción Humana de Canarias, La Laguna, Tenerife, Spain
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Reprod Sci. 2016 Dec;23(12):1644-1655. doi: 10.1177/1933719116672588.
This contribution summarizes the pivotal role of the ovarian renin-angiotensin system (OVRAS) in ovarian physiology and disease, with particular emphasis on human clinical implications and established translational applications. The presence of a complete OVRAS in all studied species has been known for decades. The OVRAS has major effects on follicle development/atresia and ovulation and steroid hormone secretion, that is, it is necessary for normal reproduction. It is well established that OVRAS activity is regulated by gonadotropins and depends on activation of proteases in the area of growing follicles. Angiotensin and angiotensin receptors are widely distributed in the ovarian follicle, preovulatory theca and granulosa cells, and postovulatory mural granulosa-lutein cells and regulate steroidogenesis. Molecular blockade of the OVRAS inhibits oocyte maturation and ovulation. Pathologically abnormal OVRAS function has been associated with infertility, polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), and ovarian cancer. Both hyperandrogenism in PCOS and third space fluid accumulation in OHSS have been convincingly linked to overexpression of renin and angiotensin. Blockade of angiotensin receptors is under study for the treatment of gynecologic cancer, OHSS, and PCOS. However, a full understanding of the OVRAS and translational applications is lacking. In part, this is due to the discovery in recent years of previously unknown renin-angiotensin system (RAS) components and novel functions of "classical" RAS components that remain to be integrated into translational studies; newer, more specific agents to block RAS components are available only now for such research and treatment. The need for further studies is evident.
本文总结了卵巢肾素 - 血管紧张素系统（OVRAS）在卵巢生理和疾病中的关键作用，特别强调了其对人类临床的影响以及已确立的转化应用。数十年来，人们已知在所有研究的物种中都存在完整的OVRAS。OVRAS对卵泡发育/闭锁、排卵和甾体激素分泌有主要影响，也就是说，它是正常生殖所必需的。众所周知，OVRAS的活性受促性腺激素调节，并依赖于生长卵泡区域蛋白酶的激活。血管紧张素和血管紧张素受体广泛分布于卵巢卵泡、排卵前的卵泡膜细胞和颗粒细胞，以及排卵后的壁颗粒黄体细胞中，并调节甾体激素生成。对OVRAS的分子阻断会抑制卵母细胞成熟和排卵。病理状态下OVRAS功能异常与不孕、多囊卵巢综合征（PCOS）、卵巢过度刺激综合征（OHSS）和卵巢癌有关。PCOS中的高雄激素血症和OHSS中的第三间隙液体积聚都已令人信服地与肾素和血管紧张素的过度表达相关联。血管紧张素受体阻断剂正在研究用于治疗妇科癌症、OHSS和PCOS。然而，对OVRAS及其转化应用仍缺乏全面的了解。部分原因是近年来发现了以前未知的肾素 - 血管紧张素系统（RAS）成分以及“经典”RAS成分的新功能，这些仍有待整合到转化研究中；用于阻断RAS成分的更新、更特异的药物现在才可用于此类研究和治疗。进一步研究的必要性显而易见。
