title: Endotoxin inhibits pituitary responsiveness to gonadotropin-releasing hormone.
abstract: Immune/inflammatory challenges powerfully suppress reproductive neuroendocrine activity. This inhibition is generally considered to be centrally mediated via mechanisms that regulate GnRH secretion. The present study provides two lines of evidence that bacterial endotoxin, a commonly used model of immune/inflammatory challenge, also acts to inhibit pituitary responsiveness to GNRH: In the first experiment, pulsatile secretion of GnRH into pituitary portal blood and LH into peripheral blood were monitored in ovariectomized ewes treated with a low dose of endotoxin. Although this treatment only marginally suppressed GnRH pulsatile secretion, it markedly disrupted LH pulsatility. In extreme cases, the low dose of endotoxin blocked LH pulses without inhibiting endogenous GnRH pulses, thereby uncoupling GnRH and LH pulsatile suppression. In the second experiment, we tested the hypothesis that endotoxin inhibits pituitary responsiveness to exogenous GnRH pulses. Hourly pulses of GnRH were delivered to ovariectomized ewes in which endogenous GnRH secretion was blocked. Endotoxin suppressed the amplitude of GnRH-induced LH pulses. Together, these observations support the conclusion that endotoxin inhibits pituitary responsiveness to GNRH:
authors.affiliation: Reproductive Sciences Program and Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Williams
authors.forename: T G
authors.initials: TG
authors.lastname: Harris
authors.forename: D F
authors.initials: DF
authors.lastname: Battaglia
authors.forename: C
authors.initials: C
authors.lastname: Viguié
authors.forename: F J
authors.initials: FJ
authors.lastname: Karsch
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects*; D012756:Sheep
chemical_list: D004731:Endotoxins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone