Cited by 1,857Estrogen and related hormone effectsBreast Cancer Treatment StudiesEffects and risks of endocrine disrupting chemicals

Estrogen receptors: how do they signal and what are their targets

Heldring, Nina, Pike, Ashley, Andersson, Sandra, Matthews, Jason, Cheng, Guojun, Hartman, Johan, Tujague, Michel, Ström, Anders +3 more·2007·Physiological Reviews

Abstract

During the past decade there has been a substantial advance in our understanding of estrogen signaling both from a clinical as well as a preclinical perspective. Estrogen signaling is a balance between two opposing forces in the form of two distinct receptors (ER alpha and ER beta) and their splice variants. The prospect that these two pathways can be selectively stimulated or inhibited with subtype-selective drugs constitutes new and promising therapeutic opportunities in clinical areas as diverse as hormone replacement, autoimmune diseases, prostate and breast cancer, and depression. Molecular biological, biochemical, and structural studies have generated information which is invaluable for the development of more selective and effective ER ligands. We have also become aware that ERs do not function by themselves but require a number of coregulatory proteins whose cell-specific expression explains some of the distinct cellular actions of estrogen. Estrogen is an important morphogen, and many of its proliferative effects on the epithelial compartment of glands are mediated by growth factors secreted from the stromal compartment. Thus understanding the cross-talk between growth factor and estrogen signaling is essential for understanding both normal and malignant growth. In this review we focus on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.

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Registry

Crossref · 10.1152/physrev.00026.2006

Cites

338 of 338 references verified0 citation errors · 0 not checkable

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  • ERα and ERβ are estrogen-responsive nuclear receptors that act as transcriptional regulators.

    “Whereas ERα and ERβ are estrogen-responsive nuclear receptors that act as transcriptional regulators24,”
  • Gonadal steroids can affect cell physiology over the long term by acting as transcription factors to regulate gene expression or rapidly through non-genomic second messenger cascades.

    “can affect cell physiology over the long term by acting as transcription factors to regulate gene expression (Heldring et al., 2007) or rapidly through non-genomic second messenger cascades (Micevych and Dominguez, 2009)”
  • The rise in either androgens or estrogens at puberty in both sexes may activate frontal cortex ERbeta, which may act as a transcription factor to alter gene expression that may then regulate the physiological properties of PV+ interneurons and change network inhibition.

    “Thus, the rise in either androgens or estrogens at puberty in both sexes may activate frontal cortex ERbeta where it may act as a transcription factor (Heldring et al., 2007) to alter gene expression that may then regulate the physiological properties of PV+ interneurons and change network inhibition.”

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Authors
Heldring, N., Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Ström, A., Treuter, E., Warner, M., & Gustafsson, J.-Å.
Affiliations
  • Karolinska Institutet (SE)
  • Houston Methodist (US)
Venue
Physiological Reviews
Published
2007-07
Volume
87
Issue
3
Pages
905-931
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W2121454015
Cited by
1,857
References
338
Citations by year
2026: 53 · 2025: 73 · 2024: 90 · 2023: 88 · 2022: 90 · 2021: 127 · 2020: 80 · 2019: 119 · 2018: 112 · 2017: 122 · 2016: 112 · 2015: 111 · 2014: 120 · 2013: 124 · 2012: 105
FWCI
8.13
Type
journal article
Language
en
Open access
closed
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
estrogen receptor, estrogen signaling, estrogen receptor alpha, estrogen receptor beta, splice variants, coregulators, morphogens, breast cancer, prostate cancer, hormone replacement therapy, autoimmune disease, depression
MeSH terms
Animals, Estrogens, Female, Humans, Receptors, Estrogen, Signal Transduction, Protein Isoforms

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