ArticleMolecular endocrinology (Baltimore, Md.)2015
Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- GPRC6A-Duox1 Axis Regulates the Hair Cycle Through HTissue engineering and regenerative medicine · 2026Article
- Testosterone and cancers: biological functions, molecular mechanisms and therapy.Molecular cancer · 2026Review
- Article
- Sex differences in innate immune cell responses: Impact on cancer immunity and response to therapy.Frontiers in immunology · 2026Review
- Nutrient sensing receptor GPRC6A regulates mTORC1 signaling and Tau biology.Neurobiology of disease · 2025Article
- Role of Testosterone Signaling in Microglia: A Potential Role for Sex-Related Differences in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic-pituitary-gonadal axis activation in Klinefelter syndrome.Journal of endocrinological investigation · 2024Article
- Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.Development (Cambridge, England) · 2024Article
- Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling.FASEB bioAdvances · 2024Article
- GPRC6A is a Potential Therapeutic Target for Metformin Regulation of Glucose Homeostasis in Mice.bioRxiv : the preprint server for biology · 2024Article
- Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia.Current issues in molecular biology · 2024Review
- 'Toxic Masculinity': What Is Known about the Role of Androgen Receptors in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2023Review
- Untargeted Metabolomics Reveals the Function of GPRC6A in Amino Acid and Lipid Metabolism in Mice.Metabolites · 2022Article
- Undercarboxylated, But Not Carboxylated, Osteocalcin Suppresses TNF-α-Induced Inflammatory Signaling Pathway in Myoblasts.Journal of the Endocrine Society · 2022Article
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.Endocrinology · 2021Review
- Binding of Androgen- and Estrogen-Like Flavonoids to Their Cognate (Non)Nuclear Receptors: A Comparison by Computational Prediction.Molecules (Basel, Switzerland) · 2021Article
- The carboxylation status of osteocalcin has important consequences for its structure and dynamics.Biochimica et biophysica acta. General subjects · 2021Review
- Sex Hormones and Lung Inflammation.Advances in experimental medicine and biology · 2021Article
- Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A.International journal of endocrinology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin. GPRC6A plays an important role in the regulation of testosterone (T) production and energy metabolism in mice. T has rapid, transcription-independent (nongenomic) effects that are mediated by a putative GPCR. We previously found that T can activate GPRC6A in vitro, but the possibility that T is a ligand for GPRC6A remains controversial. Here, we demonstrate direct T binding to GPRC6A and construct computational structural models of GPRC6A that are used to identify potential binding poses of T. Mutations of the predicted binding site residues were experimentally found to block T activation of GPRC6A, in agreement with the modeling. Using Gpr6ca(-/-) mice, we confirmed that loss of GPRC6A resulted in loss of T rapid signaling responses and elucidated several biological functions regulated by GPRC6A-dependent T rapid signaling, including T stimulation of insulin secretion in pancreatic islets and enzyme expression involved in the biosynthesis of T in Leydig cells. Finally, we identified a stereo-specific effect of an R-isomer of a selective androgen receptor modulator that is predicted to bind to and shown to activate GPRC6A but not androgen receptor. Together, our data show that GPRC6A directly mediates the rapid signaling response to T and uncovers previously unrecognized endocrine networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.