Cited by 186Receptor Mechanisms and SignalingEstrogen and related hormone effectsProstate Cancer Treatment and Research

GPRC6A Mediates the Non-genomic Effects of Steroids

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Pi, Min, Parrill, Abby L., Quarles, L. Darryl·2010·Journal of Biological Chemistry

Abstract

The identity of the putative G-protein coupled receptor (GPCR) that mediates the non-genomic effects of androgens is unknown. We present in vitro and in vivo evidence that the orphan GPRC6A receptor, a widely expressed calcium and amino acid sensing GPCR, transduces the non-genomic effects of testosterone and other steroids. Overexpression of GPRC6A imparts the ability of extracellular testosterone to illicit a rapid, non-genomic signaling response in HEK-293 cells lacking the androgen receptor. Conversely, testosterone-stimulated rapid signaling and phosphorylation of ERK is attenuated in bone marrow stromal cells derived from GPRC6A(-/-) mice and in 22Rv1 prostate cancer cells after siRNA-mediated knockdown of GPRC6A. Compared with wild-type controls, GPRC6A(-/-) null mice exhibit significantly less ERK activation and Egr-1 expression in both bone marrow and testis in response to pharmacological doses of testosterone in vivo. In addition, testosterone administration results in suppression of luteinizing hormone in wild-type male mice, but paradoxically stimulates serum luteinizing hormone levels in GPRC6A(-/-) null mice. These results suggest that GPRC6A is functionally important in regulating non-genomic effects of androgens in multiple tissues.

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  1. Zhu, Y., Rice, C. D., Pang, Y., Pace, M., and Thomas, P. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 2231-2236
  2. Bernhagen, J., Krohn, R., Lue, H., Gregory, J. L., Zernecke, A., Koenen, R. R., Dewor, M., Georgiev, I., Schober, A., Leng, L., Kooistra, T., Fin- gerle-Rowson, G., Ghezzi, P., Kleemann, R., McColl, S. R., Bucala, R., GPRC6A, an Anabolic G-protein Coupled Receptor DECEMBER 17, 2010 • VOLUME 285 • NUMBER 51 JOURNAL OF BIOLOGICAL CHEMISTRY 39963
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Authors
Pi, M., Parrill, A. L., & Quarles, L. D.
Affiliations
  • University of Tennessee Health Science Center (US)
  • University of Memphis (US)
Corresponding author
  • Pi, Min
  • Quarles, L. Darryl
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-12
Volume
285
Issue
51
Pages
39953-39964
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2132960194
Cited by
186
References
76
Citations by year
2026: 12 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 13 · 2021: 12 · 2020: 15 · 2019: 13 · 2018: 13 · 2017: 20 · 2016: 16 · 2015: 9 · 2014: 10 · 2013: 15 · 2012: 14
FWCI
4.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AR37308, RR017686)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR-37308, R01AR037308)
  • National Center for Research Resources (P20RR017686)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • 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
Keywords
GPRC6A, non-genomic steroid action, testosterone, androgens, orphan G protein-coupled receptor, ERK activation, EGR1, luteinizing hormone, mesenchymal stem cells, prostate cancer cells, calcium-sensing receptor
MeSH terms
Animals, Enzyme Activation, Humans, Male, Testosterone, Signal Transduction, Mice, Knockout, Receptors, G-Protein-Coupled, Cell Line, Tumor, Extracellular Signal-Regulated MAP Kinases, Mice, HEK293 Cells

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