EVIDENCE THAT THE MEDIOBASAL HYPOTHALAMUS IS THE PRIMARY SITE OF ACTION OF ESTRADIOL IN INDUCING THE PREOVULATORY GONADOTROPIN-RELEASING-HORMONE SURGE IN THE EWE

Although a neural site of action for estradiol in inducing a LH surge via a surge of GnRH is now well established in sheep, the precise targ et(s) for estrogen within the brain is unknown. To address this issue, two experiments were conducted during the breeding season using an ar tificial model of the follicular phase. In the first experiment, bilat eral 17 beta-estradiol microimplants were positioned in either the med ial preoptic area (MPOA) or the mediobasal hypothalamus (MBH), and LH secretion was monitored. An initial negative feedback inhibition of LH secretion was observed in ewes that had estradiol microimplants locat ed in the MPOA (6 of 6 ewes) or caudal MBH in the vicinity of the arcu ate nucleus (4 of 4). In contrast, a normal LH surge was only found in animals bearing estradiol microimplants in the MBH (5 of 10). Detaile d analysis of estradiol microimplant location with respect to the estr ogen receptor-alpha-immunoreactive cells of the hypothalamus revealed that 4 of the 5 ewes exhibiting a LH surge had microimplants located b ilaterally within or adjacent to the area of estrogen receptor-express ing cells of the ventromedial nucleus. Two of these ewes exhibited a L H surge without showing any form of estrogen negative feedback. In the second experiment, we used the technique of hypophyseal portal blood collection to monitor GnRH secretion directly at the time of the LH su rge induced by estradiol delivered either centrally or peripherally. C entral estradiol implants induced the GnRH surge. The duration and mea n plasma concentration of GnRH during the surge were not different bet ween animals given peripheral or central MBH estradiol implants. Chole sterol-filled MBH microimplants did not evoke a GnRH surge. We conclud e that the ventromedial nucleus is the primary site of action for estr adiol in stimulating the preovulatory GnRH surge of the ewe, whereas t he MPOA and possibly the caudal MBH are sites at which estrogen can ac t to inhibit LH secretion. These data provide evidence for the sites w ithin the ovine hypothalamus responsible for mediating the bimodal inf luence of estradiol on GnRH secretion and suggest that different, and possibly independent, neuronal cell populations are responsible for th e negative and positive feedback actions of estradiol.