Estrogen receptor beta regulates sexually dimorphic neural responses to estradiol

Estrogen receptors (ERs) mediate many sexual dimorphisms in the neuroendocr ine system and in behavior. We examined the consequences of the loss of fun ctional estrogen receptor beta (ER beta) on two sexually differentiated neu ral responses to estrogen. In wild type (WT) male mice, but not in females, estradiol (E-2) treatment decreased estrogen receptor a immunoreactive (ER alpha -ir) cell numbers in the arcuate nucleus (ARC), the preoptic area (P OA), and the ventromedial nucleus (VMN). These sex differences were reverse d in ERP knockout (ER beta KO) mice. Castrated ER beta KOs did not show any change in ER alpha -ir cell number after Eg treatment. Yet, E-2 decreased ER alpha -ir cell number in ovariectomized ER beta KOs. Estradiol treatment increased progesterone receptor immunoreactive (PR-ir) cell number in WT f emale VMN and POA, but no change was noted in brains of WT castrates. In ER beta KO mice the opposite relationship was found, E-2 treatment increased PR-ir cell number in male, but not in female, brains. Our results show that ERP influences several sexually dimorphic neural responses to estrogen. Mo reover the data clearly show that ERP can modulate neural expression of ER alpha.