Interaction of estrogen receptor-alpha ligand binding domain with nuclear proteins of aging mouse brain

After the interaction of estrogen with the ligand binding domain (LBD) of mouse estrogen receptor-alpha (mERalpha) and hormone-responsive elements of target genes, many nuclear proteins are recruited to regulate the expression of specific genes. Because it is not known which brain proteins interact with LBD or whether these proteins vary with age and sex, we used pull-down assay and far Western blotting to detect five nuclear proteins of 160, 140, 87, 60, and 46 kD in the mouse brain. These interacting proteins were identified as PELP1, RIP140, PGC1alpha, BAF60, and ADA3, respectively. The level of PELP1, RIP140, PGC1alpha, and BAF60 decreased drastically in old compared with adult male mice, whereas the ADA3 level showed no significant change. PELP1, PGC1alpha, and BAF60 levels were lower in old male compared with female mice. Thus we report the identification and interaction of five nuclear proteins with mERalpha-LBD, indicating their role in estrogen signaling and brain functions during aging.