The ability of estradiol to induce fos expression in a subset of estrogen receptor-alpha-containing neurons in the preoptic area of the ewe depends on reproductive status

In the ewe, seasonal anestrus results from a change in the hypothalamic res ponsiveness to estradiol (E-2) negative feedback. Considerable evidence has implicated a specific group of dopaminergic neurons (the A15 group) in thi s seasonally dependent E-2 effect, but these neurons do not appear to conta in estrogen receptor-alpha (ER alpha). This apparent discrepancy raises the possibility that at least one other neural system is also involved in medi ating E-2 inhibition. The purpose of this study was to determine whether ER alpha-containing neurons are activated by the negative feedback action of E-2 in anestrus. In Exp 1, we examined the effects of E-2 on expression of the immediate ear ly gene products, Fos and Fos-related antigens, in ER alpha-positive cells in anestrous ewes. ER alpha and Fos/ Fos-related antigens were colocalized using a dual immunofluorescence procedure in sections throughout the hypoth alamus from ovariectomized and E-2-treated ovariectomized anestrous ewes. A low dose E-2 treatment that inhibited LH pulse frequency and induced Fos i n A15 dopaminergic neurons in a previous study significantly increased the percentage of ER alpha-containing neurons expressing Fos (17.8% vs. 1.7%) i n 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 E-2 on Fos/ER alpha colocalization in this region. E-2 treatment produced a 3-f old increase in the percentage of ER alpha-positive cells expressing Fos (1 5.1% vs. 3.4%) in anestrus, but failed to increase ER alpha/Fos colocalizat ion (1.8% vs. 3.5%) during the breeding season. These data raise the possib ility that a subset of ER alpha-containing neurons in the medial preoptic a rea plays a role in the seasonal change in response to E-2 negative feedbac k in the ewe.