GPRC6A Mediates the Non-genomic Effects of Steroids
Open accessAbstract
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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Testosterone mediates nongenomic effects via a calcium and amino acid sensing GPCR (GPRC6A).
“Testosterone mediates nongenomic effects via a calcium and amino acid sensing GPCR (GPRC6A) [22].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [22]
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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)
- PMC
- PMC3000977
- 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
- hybrid
- doi.org
- Licence
- 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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