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.
Highlights
luteinizing hormone (LH) stimulates the theca cells of the ovarian follicle, leading to androgen synthesis. Some of these are bound to sex-hormone-binding globulin (SHBG), and some androgens spread to nearby granulosa cells (GCs), where they are converted to estrogen under the stimulation of follicle-stimulating hormone (FSH)
It is generally believed that disorders of the hypothalamic–pituitary–ovary axis are a significant cause of cystic formation, the cystic follicle maintains a static condition without degeneration after ovulation failure, which is considered another reason for the development of cysts [54]
Clomiphene citrate is an oral selective estrogen receptor modulators (SERMs) consisting of two isomers, zuclomiphene and enclomiphene, which compete for receptor binding sites with endogenous estrogens
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Polycystic ovary syndrome (PCOS) is a type of general disease in women that is associated with a variety of reproductive and metabolic disorders [1]. LH stimulates the theca cells of the ovarian follicle, leading to androgen synthesis Some of these are bound to sex-hormone-binding globulin (SHBG), and some androgens spread to nearby granulosa cells (GCs), where they are converted to estrogen under the stimulation of FSH. This causes an increase in the level of estrogen hormones, which in turn generates positive feedback in the form of LH production, causing a surge in LH and triggering ovulation [10]. We will discuss the latest advances in the understanding of how ER mediates the role of estrogen in polycystic ovary syndrome, with an outlook for possible clinical treatments
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