The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions

Heinlein, Cynthia A.; Chang, Chawnshang

doi:10.1210/me.2002-0070

Cited by 568Estrogen and related hormone effectsProstate Cancer Treatment and ResearchHormonal and reproductive studies

The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions

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Heinlein, Cynthia A., Chang, Chawnshang·2002·Molecular Endocrinology

DOI 10.1210/me.2002-0070

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Abstract

The biological activity of testosterone and dihydrotestosterone is thought to occur predominantly through binding to the androgen receptor (AR), a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor. However, androgens have also been reported to induce the rapid activation of kinase-signaling cascades and modulate intracellular calcium levels. These effects are considered to be nongenomic because they occur in cell types that lack a functional AR, in the presence of inhibitors of transcription and translation, or are observed to occur too rapidly to involve changes in gene transcription. Such nongenomic effects of androgens may occur through AR functioning in the cytoplasm to induce the MAPK signal cascade. In addition, androgens may function through the sex hormone binding globulin receptor and possibly a distinct G protein-coupled receptor to activate second messenger signaling mechanisms. The physiological effect of nongenomic androgen action has yet to be determined. However, it may ultimately contribute to regulation of transcription factor activity, including mediation of the transcriptional activity of AR.

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Investigations into the non-genomic actions of the androgen receptor have been limited to in vitro studies rather than in vivo due to the lack of an appropriate animal model that can distinguish between genomic and non-genomic receptor actions.
“Investigations into the non-genomic actions of the androgen receptor have been limited to in vitro studies [75, 76] rather than in vivo due to the lack of an appropriate animal model that can distinguish between genomic and non-genomic receptor actions [75].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [76]
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Authors: Heinlein, C. A., & Chang, C.
Affiliations: George Whipple Laboratory for Cancer Research, Departments of Pathology (C.A.H., C.C.), Rochester, New York 14642
University of Rochester Medicine (US)
Corresponding author: Chang, Chawnshang
ORCID: Chang, Chawnshang
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 2002-10-01
Volume: 16
Issue: 10
Pages: 2181-2187
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/me.2002-0070
OpenAlex: W2146352944
Cited by: 568
References: 76
Citations by year: 2026: 6 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 15 · 2021: 26 · 2020: 20 · 2019: 28 · 2018: 20 · 2017: 24 · 2016: 32 · 2015: 18 · 2014: 20 · 2013: 43 · 2012: 31
FWCI: 2.59
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Molecular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: University of Rochester
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: androgen receptor, androgen-binding protein, sex hormone-binding globulin, dihydrotestosterone, testosterone, MAPK signaling, intracellular calcium signaling, G protein-coupled receptors, nuclear receptor superfamily, transcriptional regulation
MeSH terms: Androgen-Binding Protein, Androgens, Animals, Cell Membrane, Humans, Receptors, Androgen, Sex Hormone-Binding Globulin, Transcription, Genetic, Protein Biosynthesis, Genome, MAP Kinase Signaling System

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The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions

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