Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Feb;56(2):R55-71.
doi: 10.1530/JME-15-0254.

What's new in estrogen receptor action in the female reproductive tract

Sylvia C Hewitt  1 , Wipawee Winuthayanon  1 , Kenneth S Korach  2
Affiliations
Review

What's new in estrogen receptor action in the female reproductive tract

Sylvia C Hewitt et al. J Mol Endocrinol. 2016 Feb.

Abstract

Estrogen receptor alpha (ERα) is a critical player in development and function of the female reproductive system. Perturbations in ERα response can affect wide-ranging aspects of health in humans as well as in livestock and wildlife. Because of its long-known and broad impact, ERα mechanisms of action continue to be the focus on cutting-edge research efforts. Consequently, novel insights have greatly advanced understanding of every aspect of estrogen signaling. In this review, we attempt to briefly outline the current understanding of ERα mediated mechanisms in the context of the female reproductive system.

Keywords: estrogen receptors; gene expression; gene regulation; hormone action; uterus/endometrium.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of ERα and ERβ protein with functional domains. Estrogen receptors ERα and ERβ share a conserved domain structure. The A/B domain, at the amino terminus (N) of the protein contains activation function 1 (AF1). The C domain binds to DNA motifs called estrogen responsive elements (EREs). The D domain is called the hinge region, and contributes to DNA binding specificity and nuclear localization of the ERs. The E domain is called the ligand binding domain because it interacts with estrogen, through an arrangement of 11 α helices (H1, and H3 through H12). H12 in this region of the receptor is critical to mediating transcriptional activation via activation function 2 (AF2). At the carboxy terminus (C) is the F domain. The % homology shared between ERα and ERβ in the C and E domains is shown.
Figure 2
Figure 2
Ligand-dependent and ligand-independent nuclear receptor mechanisms. The direct “classic” model of estrogen receptor (ER) action involves direct interaction between ER bound to estrogen (triangles) and ERE; the tethered pathway utilizes indirect “tethering” of ER to genes via interactions with other transcription factors (TF). “Nongenomic” signaling is initiated by membrane-localized receptors modulating extranuclear second messenger (SM) signaling pathways. Ligand-independent responses occur as a result of transduction of membrane receptor signaling, such as growth factors (GF), to nuclear ER. Reproduced, with permission, from Binder AK, Winuthayanon W, Hewitt SC, Couse JF & Korach KS (2015) Steroid receptors in the uterus and ovary. In Knobil and Neill's Physiology of Reproduction, 4th Edn, pp 1099–1193. Eds TM Plant & AJ Zeleznik. Elsevier.
Figure 3
Figure 3
Model of chromatin dynamics in ER mediated transcription. FoxA1 interacts with chromatin, providing access for ER to nearby EREs. ER then interacts with transcriptional co-activators and chromatin modifying enzymes to open up transcription start sites (TSS) for RNA polymerase II (PolII), allowing initiation of transcription. Reproduced, with permission, from Wall EH, Hewitt SC, Case LK, Lin CY, Korach KS & Teuscher C (2014) The role of genetics in estrogen responses: a critical piece of an intricate puzzle. FASEB Journal 28 5042–5054.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aagaard MM, Siersbaek R, Mandrup S. Molecular basis for gene-specific transactivation by nuclear receptors. Biochimica Et Biophysica Acta-Molecular Basis of Disease. 2011;1812:824–835. - PubMed
    1. Abot A, Fontaine C, Raymond-Letron I, Flouriot G, Adlanmerini M, Buscato M, Otto C, Berges H, Laurell H, Gourdy P, et al. The AF-1 activation function of estrogen receptor alpha is necessary and sufficient for uterine epithelial cell proliferation in vivo. Endocrinology. 2013;154:2222–2233. - PubMed
    1. Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, et al. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A. 2014;111:E283–290. - PMC - PubMed
    1. Ahlbory-Dieker DL, Stride BD, Leder G, Schkoldow J, Trolenberg S, Seidel H, Otto C, Sommer A, Parker MG, Schutz G, et al. DNA binding by estrogen receptor-alpha is essential for the transcriptional response to estrogen in the liver and the uterus. Molecular Endocrinology. 2009;23:1544–1555. - PMC - PubMed
    1. Andrade PM, Silva I, Borra RC, de LGR, Baracat EC. Estrogen regulation of uterine genes in vivo detected by complementary DNA array. Hormone and Metabolic Research. 2002;34:238–244. - PubMed

Publication types

LinkOut - more resources