| First Author | Pang TP | Year | 2012 |
| Journal | Mol Cell Endocrinol | Volume | 348 |
| Issue | 1 | Pages | 189-97 |
| PubMed ID | 21872641 | Mgi Jnum | J:184106 |
| Mgi Id | MGI:5320260 | Doi | 10.1016/j.mce.2011.08.017 |
| Citation | Pang TP, et al. (2012) A physiological role for androgen actions in the absence of androgen receptor DNA binding activity. Mol Cell Endocrinol 348(1):189-97 |
| abstractText | We tested the hypothesis that androgens have physiological actions via non-DNA binding-dependent androgen receptor (AR) signaling pathways in males, using our genetically modified mice that express a mutant AR with deletion of the 2nd zinc finger of the DNA binding domain (AR(DeltaZF2)) that cannot bind DNA. In cultured genital skin fibroblasts, the mutant AR(DeltaZF2) has normal ligand binding ability, phosphorylates ERK-1/2 in response to 1 min DHT treatment (blocked by the AR antagonist bicalutamide), but has reduced androgen-dependent nuclear localization compared to wildtype (WT). AR(DeltaZF2) males have normal baseline ERK-1/2 phosphorylation, with a 1.5-fold increase in Akt phosphorylation in AR(DeltaZF2) muscle vs WT. To identify physiological actions of non-DNA binding-dependent AR signaling, AR(DeltaZF2) males were treated for 6 weeks with dihydrotestosterone (DHT). Cortical bone growth was suppressed by DHT in AR(DeltaZF2) mice (6% decrease in periosteal and 7% decrease in medullary circumference vs untreated AR(DeltaZF2) males). In conclusion, these data suggest that non-DNA binding dependent AR actions suppress cortical bone growth, which may provide a mechanism to fine-tune the response to androgens in bone. |
