Back to Search
Start Over
GPRC6A Mediates the Non-genomic Effects of Steroids.
- Source :
-
Journal of Biological Chemistry . 12/17/2010, Vol. 285 Issue 51, p39953-39964. 12p. - Publication Year :
- 2010
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANDROGENS
*TESTOSTERONE
*RODENTS
*GONADOTROPIN
*LUTEINIZING hormone
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 285
- Issue :
- 51
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 64446241
- Full Text :
- https://doi.org/10.1074/jbc.M110.158063