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The Ability of Estradiol to Induce Fos Expression in a Subset of Estrogen Receptor--Containing Neurons in the Preoptic Area of the Ewe Depends on Reproductive Status¹

Department of Physiology, West Virginia University Health Sciences Center (I.S., B.A., R.L.G.), Morgantown, West Virginia 26506-9229; and the Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine (H.T.J., M.N.L.), Cincinnati, Ohio 45267-0521

Address all correspondence and requests for reprints to: Dr. Robert L. Goodman, Department of Physiology, West Virginia University Health Sciences Center, P.O. Box 9229, Morgantown, West Virginia 26506-9229. E-mail: rgoodman{at}wvu.edu

In the ewe, seasonal anestrus results from a change in the hypothalamic responsiveness to estradiol (E₂) negative feedback. Considerable evidence has implicated a specific group of dopaminergic neurons (the A15 group) in this seasonally dependent E₂ effect, but these neurons do not appear to contain estrogen receptor- (ER). This apparent discrepancy raises the possibility that at least one other neural system is also involved in mediating E₂ inhibition. The purpose of this study was to determine whether ER-containing neurons are activated by the negative feedback action of E₂ in anestrus.

In Exp 1, we examined the effects of E₂ on expression of the immediate early gene products, Fos and Fos-related antigens, in ER-positive cells in anestrous ewes. ER and Fos/ Fos-related antigens were colocalized using a dual immunofluorescence procedure in sections throughout the hypothalamus from ovariectomized and E₂-treated ovariectomized anestrous ewes. A low dose E₂ treatment that inhibited LH pulse frequency and induced Fos in A15 dopaminergic neurons in a previous study significantly increased the percentage of ER-containing neurons expressing Fos (17.8% vs. 1.7%) in the medial preoptic area, but not in other hypothalamic areas. In Exp 2, we determined whether there was a seasonal difference in the effect of E₂ on Fos/ER colocalization in this region. E₂ treatment produced a 3-fold increase in the percentage of ER-positive cells expressing Fos (15.1% vs. 3.4%) in anestrus, but failed to increase ER/Fos colocalization (1.8% vs. 3.5%) during the breeding season. These data raise the possibility that a subset of ER-containing neurons in the medial preoptic area plays a role in the seasonal change in response to E₂ negative feedback in the ewe.

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