Mechanisms for endotoxin-induced disruption of ovarian cyclicity: observations in sheep.

This review summarizes a series of experiments that address mechanisms by which endotoxin, a commonly used model of immune/inflammatory challenge, disrupts the oestrous cycle of the ewe. Initial studies in ovariectomized ewes demonstrated that endotoxin inhibits pulsatile LH secretion and that this suppression is achieved in two ways: (i) decreased episodic secretion of GnRH and (ii) reduced pituitary responsiveness to GnRH. These findings led to the hypothesis that the inhibition of pulsatile LH secretion can account for the disruptive effects of endotoxin on the oestrous cycle. Follow-up studies to test this hypothesis revealed that suppression of LH pulsatility during the follicular phase is clearly one means by which endotoxin disrupts the oestrous cycle. However, these studies also provided evidence that endotoxin can impair ovarian follicular responsiveness to gonadotrophin stimulation and inhibit the oestradiol-induced preovulatory LH surge. Collectively, these disturbances in hypothalamo-hypophyseal-ovarian function interrupt the preovulatory chain of events and thereby contribute to disruption of the ovarian cycle in response to this immune/inflammatory challenge.

Pattern and time course of immediate early gene expression in rat brain following acute stress.

The pattern and time course of brain activation in response to acute swim and restraint stress were examined in the rat by in situ hybridization using complementary RNA probes specific for transcripts encoding the products of the immediate early genes c-fos, c-jun and zif/268. A widespread pattern of c-fos messenger RNA expression was detected in response to these stressors; surprisingly, the expression patterns were substantially similar following both swim and restraint stress. A dramatic induction of c-fos messenger RNA was observed in numerous neo- and allocortical regions, the lateral septal nucleus, the hypothalamic paraventricular and dorsomedial nuclei, the anterior hypothalamic area, the lateral portion of the retrochiasmatic area, the medial and cortical amygdaloid nuclei, the periaqueductal gray, and the locus coeruleus; however, a prominent induction of c-fos was also seen in numerous additional subcortical and brainstem regions. Although not as widely expressed in response to stress as c-fos, induction of zif/268 messenger RNA was also detected throughout many brain areas; these regions were largely similar to those in which c-fos was induced, although in a number of regions zif/268 was expressed in regions devoid of c-fos messenger RNA. Few brain areas showed increased expression of c-jun following stress; these regions also showed induction of c-fos and/or zif/268. The time courses of expression of all three immediate early genes were similar, with peak levels observed at the 30 or 60 min time point, and a markedly reduced signal evident at 120 min post-stress. However, in a number of cases a delayed and/or prolonged induction was noted that may be indicative of secondary neuronal activation. A number of recent studies have attempted to define neural pathways which convey stress-related information to the hypothalamic-pituitary-adrenal axis. The present results reveal a widespread pattern of neuronal activation in response to acute swim or restraint stress. These findings may aid in the identification of stress-specific neural circuits and are thus likely to have important implications for our understanding of neuronal regulation of the stress response.