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Estrogen Receptor ß Modulates Estradiol Induction of Progestin Receptor Immunoreactivity in Male, But Not in Female, Mouse Medial Preoptic Area

Department of Biochemistry and Molecular Genetics (E.F.R.) and Neuroscience Graduate Program (A.E.K., E.F.R.), University of Virginia Medical School, Charlottesville, Virginia 22908; and Center for Biotechnology and Department of Medical Nutrition (J.-A.G.), Karolinska Institute, NOVUM S-141 86 Huddinge, Sweden

Address all correspondence and requests for reprints to: Emilie F. Rissman, P.O. Box 800733, University of Virginia, Medical School, Charlottesville, Virginia 22908. E-mail: rissman{at}virginia.edu.

The medial preoptic area (mPOA) of the hypothalamus contains many neurons that express estrogen receptor (ER) and/or ERß. We examined the distribution of these receptors and assessed responses to estradiol (E₂) in the adult mouse mPOA. Gonadectomized adult male and female mice were killed, and brains were processed for immunocytochemistry for ER and ERß. More ER immunoreactive (-ir) than ERß-ir neurons were present in the mouse mPOA. Numbers of ER-ir cells were equivalent between males and females, but males had significantly more ERß-ir neurons than females. Using breeders that were heterozygous for disrupted ER and ERß genes, we produced offspring with varying numbers (0, 1, or 2) of functional and disrupted ER and ERß 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 ER had reduced PR-ir cell numbers. In gonadectomized, untreated mice, one functional copy of the ERß 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 ER, whereas in males, at least a single copy of both functional ERß and ER 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.

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