| First Author | Shihan M | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1843 |
| Issue | 6 | Pages | 1172-81 |
| PubMed ID | 24631506 | Mgi Jnum | J:211555 |
| Mgi Id | MGI:5575675 | Doi | 10.1016/j.bbamcr.2014.03.002 |
| Citation | Shihan M, et al. (2014) Non-classical testosterone signaling is mediated by a G-protein-coupled receptor interacting with Gnalpha11. Biochim Biophys Acta 1843(6):1172-81 |
| abstractText | Testosterone is known to mediate its effects by two different mechanisms of action. In the so-called "classical" pathway testosterone binds to cytosolic androgen receptors (AR), which essentially function as ligand-activated transcription factors. Once activated, these receptors bind to DNA and activate the expression of target genes. In the "non-classical" pathway, the steroid hormone binds to receptors associated with the plasma membrane and induces signaling cascades mediated through activation of Erk1/2. The precise nature of the membrane-associated AR, however, remains controversial. Although some assume that the membrane and cytosolic AR are identical, others propose that the AR of the membrane is a G-protein-coupled receptor (GPCR). To evaluate these two possibilities we first searched for testosterone-induced signaling cascades in the spermatogenic cell line GC-2. Testosterone was found to cause phosphorylation (activation) of Erk1/2, CREB, and ATF-1, consistent with its non-classical mechanism of action. Silencing of AR expression by means of siRNA did not influence testosterone-induced activation of Erk1/2, CREB, or ATF-1, indicating that this pathway is not activated by the classical cytosolic/nuclear AR. In contrast, when the expression of the G-protein Gnalpha11 is suppressed, the activation of these signaling molecules is abolished, suggesting that these responses are elicited through a membrane-bound GPCR. The results presented here and the identification of the testosterone-specific GPCR in future investigations will help to reveal and characterize new testosterone-mediated mechanisms associated not only with fertility and reproduction but perhaps also with other physiological processes. |
