Abstract
Estrogen mainly binds to estrogen receptors (ERs) to regulate menstrual cycles and reproduction. The expression of ERalpha (ERα), ERbeta (ERβ), and G-protein-coupled estrogen receptor (GPER) mRNA could be detected in ovary, suggesting that they play an important role in estrogen signal transduction in ovary. And many studies have revealed that abnormal expression of estrogen and its receptors is closely related to ovarian disease or malignant tumors. With the continuous development and research of animal models, tissue-specific roles of both ERα and ERβ have been demonstrated in animals, which enable people to have a deeper understanding of the potential role of ER in regulating female reproductive diseases. Nevertheless, our current understanding of ERs expression and function in ovarian disease is, however, incomplete. To elucidate the biological mechanism behind ERs in the ovary, this review will focus on the role of ERα and ERβ in polycystic ovary syndrome (PCOS), ovarian cancer and premature ovarian failure (POF) and discuss the major challenges of existing therapies to provide a reference for the treatment of estrogen target tissue ovarian diseases.
Highlights
In the female reproductive system, there are two major components, the uterus, which is used for pregnancy, and the ovary, which generates ova
It is well known that in the late follicular phase of the menstrual cycle when concentrations of E2 reach a persistently high critical concentration (≥ 200pg/mL), a dramatic shift occurs in E2 action, such that feedback changes from negative to positive at both pituitary and hypothalamic levels; after the shift, E2 becomes a positive inducer of the anterior pituitary and triggers it to release more follicle stimulating hormone (FSH) and luteinizing hormone (LH)
It has long been suspected that estrogen receptors (ERs) play an important role in in the ovaries, and there is strong evidence that this is the case in many models, the role of estrogen and its receptors in human disease is extraordinarily complex
Summary
In the female reproductive system, there are two major components, the uterus, which is used for pregnancy, and the ovary, which generates ova. It is well known that in the late follicular phase of the menstrual cycle when concentrations of E2 reach a persistently high critical concentration (≥ 200pg/mL), a dramatic shift occurs in E2 action, such that feedback changes from negative to positive at both pituitary and hypothalamic levels; after the shift, E2 becomes a positive inducer of the anterior pituitary and triggers it to release more FSH and LH These increased levels of FSH and LH stimulate ovarian follicles to produce more E2 [7–9]. The nuclear ER-estrogen complex can bind to ERE sequences indirectly through protein-protein interactions with transcription factors, like activator protein 1 (AP-1) or specificity protein 1 (SP-1) that occur in the promoter regions of ERE sequences These interactions result in the recruitment of co-regulatory proteins (co-activators or co-repressors) to the promoter, changes in mRNA levels, and the production of proteins that are associated with physiological responses [39–42]. Polypeptide growth factors, such as epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), activate ER and increase the expression of ER target genes in an estrogen-
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