Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary
Interactions between androgens, FSH, anti-Mullerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary
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DOI：
10.1093/humupd/dmw027
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发表时间：
2016-11-01
影响因子：
13.3
通讯作者：
Catteau-Jonard, Sophie
中科院分区：
文献类型：
--
作者：
Dewailly, Didier;Robin, Geoffroy;Catteau-Jonard, Sophie
雄激素、FSH、抗苗勒管激素（AMH）和雌二醇（E2）在人类卵巢卵泡发生中是必需的。然而，这四个球员之间的相互作用是不完全understood.本文的目的是突出雄激素，FSH，AMH和E2的外观和功能的时间顺序，并讨论FSH和AMH之间的关系的争议。通过对雄激素、FSH、FSH受体、抗苗勒管激素、AMHRII、雌二醇、卵泡、卵巢、多囊卵巢综合征、芳香化酶、颗粒细胞、卵母细胞等相关文献的检索，对多囊卵巢综合征（PCOS）的发病机制进行探讨。检索的时间段为1980-2015年，查询的数据库为PubMed和Web of Science。在窦前（“促性腺激素非依赖性”）卵泡生长期间，FSH已经活跃，并与卵泡膜细胞衍生的雄激素协同促进卵泡生长。相反，AMH通过抵消FSH而具有抑制作用。我们质疑AMH受雄激素调节的假设，并提出通过雄激素依赖性放大FSH对小卵泡颗粒细胞（GCs）的作用而间接影响。这一假设意味着FSH刺激AMH表达。在窦状卵泡（“促性腺激素依赖性”）生长期间，E2的产生是由FSH依赖性芳香化酶激活引起的。相反，AMH是抑制性的，但其表达的下降，E2放大，允许芳香化酶的充分表达，大窦卵泡的特征。我们提出了一个理论方案，由两个三角形，遵循对方的时间顺序。在PCOS中，由于内源性雄激素过多，使GC对FSH超敏，因此AMH表达过多，因此窦前卵泡过度生长（三角形1）。窦卵泡的生长和分化受到干扰（三角形2），因为AMH阻断芳香化酶，异常持续地抑制FSH的作用。除了无排卵，这种情况也可以用来解释PCOS患者对促性腺激素治疗的更高接受性和卵巢过度刺激综合征（OHSS）的风险增加。在GC中，FSH和AMH效应之间的平衡是从雄激素驱动卵泡向雌激素驱动卵泡转变的关键。我们的两个三角形假说，基于文献中的更新数据，为理解正常和多囊卵巢的卵泡发生提供了一个教学模板。它为治疗PCOS引起的无排卵开辟了新的途径。
Androgens, FSH, anti-Mullerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood.The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS).A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science.During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the abnormally persisting inhibition of FSH effects by AMH that blocks aromatase. Beside anovulation, this scenario may also serve to explain the higher receptiveness to gonadotropin therapy and the increased risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS.Within GCs, the balance between FSH and AMH effects is pivotal in the shift from androgen- to oestrogen-driven follicles. Our two triangles hypothesis, based on updated data from the literature, offers a pedagogic template for the understanding of folliculogenesis in the normal and polycystic ovary. It opens new avenues for the treatment of anovulation due to PCOS.