Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway.
Immune/inflammatory challenges, such as bacterial endotoxin, disrupt gonadotropin secretion and ovarian cyclicity. We previously determined that endotoxin can block the estradiol-induced LH surge in the ewe. Here, we investigated mechanisms underlying this suppression. First, we tested the hypothesis that endotoxin blocks the estradiol-induced LH surge centrally, by preventing the GnRH surge. Artificial follicular phases were created in ovariectomized ewes, and either endotoxin or vehicle was administered together with a surge-inducing estradiol stimulus. In each ewe in which endotoxin blocked the LH surge, the GnRH surge was also blocked. Given this evidence that endotoxin blocks the estradiol-induced LH surge at the hypothalamic level, we began to assess underlying central mechanisms. Specifically, in view of the prior demonstration that prostaglandins mediate endotoxin-induced suppression of pulsatile GnRH secretion in ewes, we tested the hypothesis that prostaglandins also mediate endotoxin-induced blockade of the surge. The prostaglandin synthesis inhibitor flurbiprofen was delivered together with endotoxin and the estradiol stimulus. Although flurbiprofen abolished endotoxin-induced fever, which is a centrally generated, prostaglandin-mediated response, it failed to reverse blockade of the LH surge. Collectively, these results indicate endotoxin blocks the LH surge centrally, suppressing GnRH secretion via a mechanism not requiring prostaglandins. This contrasts with the suppressive effect of endotoxin on GnRH pulses, which requires prostaglandins as intermediates.
Breen
Kellie M
KM
Reproductive Sciences Program, Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-0404, USA.
Billings
Heather J
HJ
Debus
Nathalie
N
Karsch
Fred J
FJ
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D005498:Follicular Phase / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000276:immunology* / Q000378:metabolism*; D010052:Ovariectomy; D011453:Prostaglandins / Q000378:metabolism*; D011673:Pulsatile Flow; D012756:Sheep; D013312:Stress, Physiological / Q000276:immunology / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D011453:Prostaglandins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D005480:Flurbiprofen; D007986:Luteinizing Hormone