Novel estrogen feedback sites associated with stress-induced suppression of luteinizing hormone secretion in female rats.

1. The fasting-induced suppression of LH secretion is totally dependent on steroidal milieu because the suppression is observed only in intact or ovariectomized estrogen-primed rats but not in ovariectomized animals. The following neural pathway mediating fasting-induced suppression of LH secretion has been suggested by a series of experiment: A neural signal emanating from the stomach during fasting reaches the medulla oblongata via afferent vagal nerve so as to activate the noradrenergic system projecting to the PVN: this results in an increased CRH release, and in turn the suppression of the LHRH release and then LH release. Estrogen seems to activate the neural pathway by acting on somewhere in the pathway. 2. We found that the paraventricular nucleus of the hypothalamus (PVN) and A2 region of the medulla oblongata is the estrogen feedback sites associated the dependence of the fasting-induced suppression of LH secretion on estrogen. The estrogen feedback action on the PVN does not involve an increase in norepinephrine release in the PVN. In addition, we also found that estrogen receptors are increased in the PVN and A2 region by acute fasting. Therefore, the following hypothesis is proposed: fasting first induces an transient increase in the activity of noradrenergic system at the beginning of the first dark phase after the food deprivation; this activation results in an increase in estrogen receptors in the PVN and A2 region; the increase in estrogen receptors leads to an increase in the sensitivity of noradrenergic systems to the neural inputs associated with fasting to these nuclei. 3. The response of the reproductive activity to various external stimuli including stress is modulated by ovarian steroids. The estrogen feedback action on the PVN and A2 is totally different from the so-called "negative feedback action" of estrogen that is for monitoring the ovarian condition. The novel estrogen feedback action may alter the response of neurons regulating gonadal axis to the signal associated with environmental cues such as stress.