Estrogen receptor β modulates estradiol induction of progestin receptor immunoreactivity in male, but not in female, mouse medial preoptic area

The medial preoptic area (mPOA) of the hypothalamus contains many neurons that express estrogen receptor α (ER) and/or ERβ. We examined the distribution of these receptors and assessed responses to estradiol (E ₂) in the adult mouse mPOA. Gonadectomized adult male and female mice were killed, and brains were processed for immunocytochemistry for ERα and ERβ. More ERα immunoreactive (-ir) than ERβ-ir neurons were present in the mouse mPOA. Numbers of ERα-ir cells were equivalent between males and females, but males had significantly more ERβ-ir neurons than females. Using breeders that were heterozygous for disrupted ERα and ERβ genes, we produced offspring with varying numbers (0, 1, or 2) of functional and disrupted ERα and ERβ genes. After gonadectomy, half the mice received E₂ for 5 d before they were killed. Estradiol treatment, sex, and genotype each had independent effects on numbers of PR-ir neurons in the mPOA. In all cases, brains that lacked at least one functional copy of ERα had reduced PR-ir cell numbers. In gonadectomized, untreated mice, one functional copy of the ERβ gene was correlated with the largest amount of PR-ir. After E₂ treatment, both sexes had greatly enhanced numbers of PR-ir containing neurons. In females, maximal PR induction required the presence of at least one functional copy of ERα, whereas in males, at least a single copy of both functional ERβ and ERα genes was needed for maximal PR-ir induction. We hypothesize that the two ERs have dependent and independent roles in sexual differentiation of neuroendocrine function.