17β-Estradiol modulates age-dependent binding of 40 kDa nuclear protein to androgen receptor promoter in mouse cerebral cortex

Abstract

Androgen influences the function of central and peripheral nervous system and plays a crucial role in maintaining reproductive behaviors and neuroendocrine regulation. Such action is mediated by interaction of androgen receptor (AR) promoter with nuclear proteins, which are involved in transcriptional regulation of androgen responsive genes. We have analyzed the binding of AR core promoter to nuclear proteins from the cerebral cortex of adult and old mice of both sexes by electrophoretic mobility shift assay (EMSA) and characterized the bound protein by Southwestern blotting. EMSA showed that the binding of nuclear proteins declined in the cerebral cortex of intact old mice as compared to adult. Following gonadectomy, the binding was reduced in old male and adult female but increased in old female. In contrast, estradiol supplementation increased the binding in old male and adult female but decreased in old female. Southwestern blotting analysis revealed that a 40 kDa nuclear protein bound to the promoter and the binding pattern was similar to that observed in EMSA. Further characterization of this protein may help to explore the intricate mechanism that underlies the transcriptional regulation of androgen responsive genes during aging.