Psychosocial stress inhibits amplitude of gonadotropin-releasing hormone pulses independent of cortisol action on the Type II glucocorticoid receptor

Elizabeth R Wagenmaker, Kellie M Breen, Amy E Oakley, Alan John Tilbrook, Fred J Karsch

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65 Citations (Scopus)


Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine if this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared to non-stressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: non-stress control, stress, and stress+the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared to non-stress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different.
Original languageEnglish
Pages (from-to)762 - 769
Number of pages7
Publication statusPublished - 2009

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