Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Endocrinology Year : 2004

Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway

Abstract

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.
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Dates and versions

hal-02680042 , version 1 (31-05-2020)

Identifiers

  • HAL Id : hal-02680042 , version 1
  • PRODINRA : 15342
  • WOS : 000187677400030

Cite

Kellie M. Breen, Heather J. Billings, Nathalie Debus, Fred J. Karsch. Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway. Endocrinology, 2004, 145 (1), pp.221-227. ⟨hal-02680042⟩
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