title: Mechanisms for endotoxin-induced disruption of ovarian cyclicity: observations in sheep.
abstract: 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.
authors.affiliation: Reproductive Sciences Program and Department of Physiology, University of Michigan, Ann Arbor, MI 48109-0404, USA. fjkarsch@umich.edu
authors.forename: F J
authors.initials: FJ
authors.lastname: Karsch
authors.forename: D F
authors.initials: DF
authors.lastname: Battaglia
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects; D007986:Luteinizing Hormone / Q000378:metabolism; D023421:Models, Animal; D010053:Ovary / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D012756:Sheep
chemical_list: D004731:Endotoxins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone