Ovarian Actions of Estrogen Receptor-β

An Update

Ann E. Drummond, Ph.D.; Peter J. Fuller, B.Med.Sci., M.B.B.S., Ph.D., F.R.A.C.P.

Disclosures

Semin Reprod Med. 2012;30(1):32-38. 

In This Article

Abstract and Introduction

Abstract

Estrogen is essential for folliculogenesis with independent roles attributed to each of the two estrogen receptors (ERs). ERβ, expressed predominantly by the ovarian granulosa cells, is required for antrum formation, preovulatory follicle maturation, expression of genes involved in ovarian differentiation (luteinizing hormone, aromatase, etc.), and follicle rupture during ovulation. Ovulatory dysfunction is associated with polymorphisms of the ERβ gene, and endocrine disruptors that selectively activate ERβ cause reproductive dysfunction and impairment fertility. ERβ may also exhibit antitumorigenic properties, with a decline in ERβ levels in epithelial ovarian cancers associated with more severe disease and poor prognosis. In this review, we examine the models that have been used to elucidate the roles ERβ plays in the ovary and consider the clinical consequences of altered ERβ expression or inappropriate activation of ERβ signaling.

Introduction

Estrogen is an essential intrafollicular modulator stimulating granulosa cell proliferation and facilitating the actions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on ovarian cells.[1] In response to FSH, granulosa cells aromatize androgens to estrogens (primarily estradiol). The actions of estrogen are transduced by estrogen receptors (ERs) ERα and ERβ. ERβ was not identified until 1996,[2,3] at which point there was a resurgence of interest in estrogen action throughout the body. Knockout mouse models were developed that either eliminated one or both of the receptors (ERα and ERβ) or prevented estrogen production (aromatase knockout mouse [ArKO]).[4–11] ERα and ERβ exhibit specific tissue localization and levels of expression. ERβ is expressed in high levels in the ovary and prostate.[12] High levels of ERα are also present in the ovary, epididymis, testis, and pituitary.[12] Despite interest in the role of ERβ in bone, the cardiovascular system, and in inflammation (summarized in a review by Harris), its role in the ovary has received very little attention.[13] Here we review what is currently known about ERβ action in the ovary, in both health and disease states.

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