Neural systems mediating the negative feedback actions of estradiol and progesterone in the ewe

The ewe shows a marked seasonal variation in the effects of ovarian steroids on pulsatile GnRH secretion. In the breeding season, progesterone inhibits GnRH pulse frequency, while estradiol suppresses pulse amplitude. In anestrus, both steroids inhibit pulse frequency. The effects of progesterone in both seasons are mediated by endogenous opioid peptides (EOP) that act in the preoptic area (POA) and medial basal hypothalamus (MBH). However, knife cut studies indicate that actions in the MBH are most important. Moreover, blockade of EOP receptors activates (e.g., induces Fos) GnRH perikarya in the MBH, but not those in the POA. Thus interactions between EOP and GnRH neurons within the MBH may be critical for progesterone negative feedback. The neural systems mediating estradiol suppression of GnRH pulse amplitude in the breeding season are largely unknown, although alpha-adrenergic neurons may be involved. The seasonal variation in inhibition of GnRH pulse frequency by estradiol is postulated to be mediated by a group of dopaminergic (DA) neurons that have three important properties: (1) they inhibit GnRH pulse frequency; (2) their activity is stimulated by estradiol; and (3) they are functional in anestrus, but not the breeding season. Recent work examining the effects of lesions of DA neurons and the ability of estradiol to induce Fos in DA cells strongly suggests that DA neurons in the retrochiasmatic area (A15) and POA (A14) have all three characteristics. We thus propose that these DA neurons are responsible for the seasonal variation in the ability of estradiol to inhibit GnRH pulse frequency.