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Review
. 2019 Sep 21;8(10):1123.
doi: 10.3390/cells8101123.

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Zi-Run Tang  1 , Rui Zhang  2 , Zheng-Xing Lian  3 , Shou-Long Deng  4 , Kun Yu  5
Affiliations
Review

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Zi-Run Tang et al. Cells. .

Abstract

Estrogen receptors (ER) include ER alpha, ER beta and new membrane receptor G protein-coupled receptor 30 (GPR30). Estrogen receptors are key receptors to maintain ovarian granulosa cell differentiation, follicle and oocyte growth and development, and ovulation function. The abnormal functions of estrogen, its receptors, and estradiol synthesis-related enzymes are closely related to clinical reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS) and endometriosis (EMS). At present, hormone therapy is the main treatment for ovarian-related diseases, and a stable hormone environment is established by regulating ovarian function. In recent years, some estrogen-related drugs have made great progress, such as clomiphene, which is a nonsteroidal antiestrogen drug in clinical application. This article elaborates on the regulatory role of estrogen and its nuclear receptors and membrane receptors in oocyte development, especially female reproductive diseases related to the abnormal expression of estrogen and its receptors. We also highlighted the latest advances of treatment strategy for these diseases and the application of related targeted small molecule drugs in clinical research and treatment, so as to provide reference for the treatment of female reproductive diseases.

Keywords: estrogen receptor; female reproductive disease; ovary.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
G-protein-coupled estrogen receptor (GPER) and agonists and antagonists of cell-membrane-bound receptors derived from estrogen receptor (ER)α and ERβ, involved in rapid intracellular signal transduction. Arrows indicate activation, blocked arrows indicate inhibition, and dashed lines indicate tissue-specific activation or inhibition.
Figure 2
Figure 2
Expression of ERβ in endometriosis. ERβ mainly participates in endometriosis through the following ways: Inhibiting TNFα-mediated apoptosis, inducing an increase in interleukin-1, and co-stimulating Ras-related and estrogen-regulated growth inhibitor (REGE) expression with prostaglandin E2 (PGE2) under the action of estradiol. In addition, serum and glucocorticoid-regulated kinases (SGK1) is a co-targeting target of PGE2 and estradiol. These pathways lead to proliferation of endometriosis cells.
Figure 3
Figure 3
Structures of synthetic therapeutic drugs: (a) diethylstilbestrol; (b) 4-hydroxytamoxifen; (c) raloxifene; and (d) ethynylestradiol.
See this image and copyright information in PMC

References

    1. Callard G.V., Tarrant A.M., Novillo A., Yacci P., Ciaccia L., Vajda S., Chuang G., Kozakov D., Greytak S.R., Sawyer S., et al. Evolutionary origins of the estrogen signaling system: Insights from amphioxus. J. Steroid Biochem. Mol. Biol. 2011;127:176–188. doi: 10.1016/j.jsbmb.2011.03.022. - DOI - PMC - PubMed
    1. Jensen E.V., Jacobson H.I. Basic guides to the mechanism of. Estrogen action. Recent Progr. Hormone Res. 1962;18
    1. Kuiper G.G., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J.A. Cloning of a novel receptor expressed in rat prostate and ovary. P. Natl. Acad. Sci. USA. 1996;93:5925–5930. doi: 10.1073/pnas.93.12.5925. - DOI - PMC - PubMed
    1. Thomas P., Pang Y., Filardo E.J., Dong J. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology. 2005;146:624–632. doi: 10.1210/en.2004-1064. - DOI - PubMed
    1. Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005;307:1625–1630. doi: 10.1126/science.1106943. - DOI - PubMed

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