A physiological role for androgen actions in the absence of androgen receptor DNA binding activity

Abstract

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 ΔZF2) that cannot bind DNA. In cultured genital skin fibroblasts, the mutant AR ΔZF2 has normal ligand binding ability, phosphorylates ERK-1/2 in response to 1min DHT treatment (blocked by the AR antagonist bicalutamide), but has reduced androgen-dependent nuclear localization compared to wildtype (WT). AR ΔZF2 males have normal baseline ERK-1/2 phosphorylation, with a 1.5-fold increase in Akt phosphorylation in AR ΔZF2..