FOS EXPRESSION DURING THE ESTRADIOL-INDUCED GONADOTROPIN-RELEASING-HORMONE (GNRH) SURGE OF THE EWE - INDUCTION IN GNRH AND OTHER NEURONS

The protein product of the protooncogene c-fos was used as a marker of cellular activation in an attempt to identify those neurons in the pr eoptic area and hypothalamus that participate in generation of the est radiol-induced surge of GnRH in the ewe. GnRH- and Fos-expressing cell s were identified immunocytochemically, and the percent of coexpressio n was determined in three states: mid-luteal phase (low GnRH release, n = 6); short-term ovariectomy (high episodic GnRH release, n = 6); an d induced GnRH surge (high sustained release, n = 8). To induce the Gn RH surge, a follicular phase rise in circulating estradiol was simulat ed in a physiological model for the estrous cycle. Serum LH was measur ed as an indicator of GnRH release. In the luteal phase, LH was basal, indicating low GnRH secretion. Few cells expressed Fos; these were no t GnRH cells. Despite high intermittent GnRH release in short-term ova riectomized ewes, GnRH cells did not express Fos. During the surge (su stained high GnRH release), 41 +/- 8% of GnRH cells expressed Fos; the se cells were dispersed throughout the field of distribution of GnRH n eurons. In addition to Fos in GnRH-positive cells, many more non-GnRH cells in the preoptic area, anterior hypothalamus, and ventrolateral h ypothalamus expressed Fos during the surge than in the luteal phase or after ovariectomy. We suggest that Fos expression in GnRH cells is ma rkedly increased by the positive feedback action of estradiol (surge), whereas short-term removal of negative feedback (ovariectomy) has lit tle, if any, effect, despite increased GnRH release in both states. Si nce estradiol induces Fos expression in far more than GnRH neurons, ou r results also suggest that estradiol activates other cells, some of w hich may be part of a neuronal chain leading to GnRH surge generation, and some of which may be related to other neural actions of estradiol , such as estrous behavior.