Estrogen receptor β regulates sexually dimorphic neural responses to estradiol

Estrogen receptors (ERs) mediate many sexual dimorphisms in the neuroendocrine system and in behavior. We examined the consequences of the loss of functional estrogen receptor β (ERβ) on two sexually differentiated neural responses to estrogen. In wild type (WT) male mice, but not in females, estradiol (E₂) treatment decreased estrogen receptor α immunoreactive (ERα-ir) cell numbers in the arcuate nucleus (ARC), the preoptic area (POA), and the ventromedial nucleus (VMN). These sex differences were reversed in ERβ knockout (ERβKO) mice. Castrated ERβKOs did not show any change in ERα-ir cell number after E₂ treatment. Yet, E₂ decreased ERα-ir cell number in ovariectomized ERβKOs. Estradiol treatment increased progesterone receptor immunoreactive (PR-ir) cell number in WT female VMN and POA, but no change was noted in brains of WT castrates. In ERβKO mice the opposite relationship was found, E₂ treatment increased PR-ir cell number in male, but not in female, brains. Our results show that ERβ influences several sexually dimorphic neural responses to estrogen. Moreover the data clearly show that ERβ can modulate neural expression of ERα.