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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) [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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Metadata
- 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 › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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