Estrogen Receptors in Polycystic Ovary Syndrome

Abstract

Female infertility is mainly caused by ovulation disorders, which affect female reproduction and pregnancy worldwide, with polycystic ovary syndrome (PCOS) being the most prevalent of these. PCOS is a frequent endocrine disease that is associated with abnormal function of the female sex hormone estrogen and estrogen receptors (ERs). Estrogens mediate genomic effects through ERα and ERβ in target tissues. The G-protein-coupled estrogen receptor (GPER) has recently been described as mediating the non-genomic signaling of estrogen. Changes in estrogen receptor signaling pathways affect cellular activities, such as ovulation; cell cycle phase; and cell proliferation, migration, and invasion. Over the years, some selective estrogen receptor modulators (SERMs) have made substantial strides in clinical applications for subfertility with PCOS, such as tamoxifen and clomiphene, however the role of ER in PCOS still needs to be understood. This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus, and the clinical application of related targeted small-molecule drugs.

ERβ Regulation of Gonadotropin Responses during Folliculogenesis

“…ERβ polymorphisms and mutations in women have been linked to ovulatory dysfunctions, including complete ovarian failure [ 147 , 148 , 149 , 150 ]. PCOS, a common clinical condition among women that causes failure of ovulation and infertility, is associated with high levels of LH and androgens [ 151 , 152 ]. Recent genomewide association studies have linked FSH and LH receptor variants to the development of PCOS [ 153 ].…”

Recent Approaches in the Treatment of Polycystic Ovary Syndrome: An Update

“…Selective Estrogen Receptor Modulators (SERMs) are antiestrogens having selectivity to stimulate or inhibit the estrogen receptor of different target tissues and show variation in the ratio of the estrogenic and antiestrogenic at other tissues [25]. Clomiphene (Figure 3) (brand name Clomid and Serophene) is a triphenylethylene-derived nonsteroidal selective estrogen receptor modulator used as an ovulationinducing drug for the last 40 years.…”

Endometrial Receptivity in Patients with Polycystic Ovary Syndrome

“…Human endometrium is a tissue whose development depends on the level of circulating hormones. During the follicular phase of the cycle, the increasing circulating estradiol levels determine the proliferation of the endometrial cells and increased endometrial sensitivity to estrogen through increasing the estrogen receptors (ER) ER-α levels [24,25]. The ER expression is highest in the late proliferative phase, decreasing in the luteal phase [25].…”

“…During the follicular phase of the cycle, the increasing circulating estradiol levels determine the proliferation of the endometrial cells and increased endometrial sensitivity to estrogen through increasing the estrogen receptors (ER) ER-α levels [24,25]. The ER expression is highest in the late proliferative phase, decreasing in the luteal phase [25]. Following ovulation, the progesterone production determines inhibition of cellular proliferation, mitotic activity, DNA synthesis and stimulates the differentiation of the endometrial cells [26].…”