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 alpha (ER) and/or ERbeta. 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 ERalpha and ERbeta. More ERalpha immunoreactive (-ir) than ERbeta-ir neurons were present in the mouse mPOA. Numbers of ERalpha-ir cells were equivalent between males and females, but males had significantly more ERalpha-ir neurons than females. Using breeders that were heterozygous for disrupted ERalpha and ERbeta genes, we produced offspring with varying numbers ( 0, 1, or 2) of functional and disrupted ERalpha and ERbeta genes. After gonadectomy, half the mice received E-2 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 ERalpha had reduced PR-ir cell numbers. In gonadectomized, untreated mice, one functional copy of the ERbeta gene was correlated with the largest amount of PR-ir. After E-2 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 ERalpha, whereas in males, at least a single copy of both functional ERbeta and ERalpha 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.