Psychosocial Stress Inhibits Amplitude of Gonadotropin-Releasing Hormone Pulses Independent of Cortisol Action on the Type II Glucocorticoid Receptor

Abstract

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 whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed 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: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress 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 that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different. (Endocrinology 150: 762-769, 2009) V arious types of stress potently stimulate the hypothalamic-pituitary-adrenal axis and simultaneously suppress reproductive neuroendocrine activity. For example, psychosocial stress increases circulating levels of glucocorticoids and inhibits pulsatile LH secretion (1-4). Recent studies in ovariectomized sheep have demonstrated that a stress-like elevation of plasma cortisol decreases pulsatile LH secretion in the absence of stress and that this occurs via suppression of pituitary responsiveness to GnRH (5-7). This effect of cortisol, which reflects a direct action on the pituitary and mediation by the type II glucocorticoid receptor (GR), occurs without concurrent inhibition of pulsatile GnRH secretion (6,8,9). Our laboratory has recently described a paradigm of psychosocial stress that consists of sequential layering of isolation, restraint, blindfold, and predator cues (barking dog sound and odor) (10). This model of psychosocial stress ("layered stress paradigm") causes a robust elevation in circulating cortisol along with a profound decrease in LH pulse amplitude and steroidinduced sexual behavior in ovariectomized ewes (10, 11). The decrease in LH pulse amplitude was observed not only in ovariectomized ewes in which LH pulses were driven by endogenous GnRH pulses, it was also evident in a pituitary-clamp model in which endogenous GnRH pulses were blocked and LH pulses were driven by fixed hourly boluses of exogenous...

Atrazine Inhibits Pulsatile Gonadotropin-Releasing Hormone (GnRH) Release Without Altering GnRH Messenger RNA or Protein Levels in the Female Rat1

“…The interaction between stress hormones and reproductive function has been known for many years (for reviews, see [36,37]). Although the mechanism by which the hypothalamic-pituitary-adrenal axis modifies the function of the hypothalamic-pituitary-gonadal (HPG) axis is not completely understood, stress hormones can act at all levels of the HPG axis [38][39][40][41][42]. High glucocorticoid levels cause decreased LH pulse frequency and increased amplitude [43].…”

Human–animal interaction, stress, and embryo production in Bos indicus embryo donors under tropical conditions

“…Breen et al (2005) found a decrease in LH pulses after administration of 30 ng/mL cortisol in sheep. This effect on LH release is also a result of a reduced GnRH pulse amplitude (Wagenmaker et al 2009). Moreover, Edwards et al (1987) observed that heifers subjected to transport stress followed by superovulation reached high cortisol concentrations and had decreased corpus luteum production.…”

The Estrous Cycle of the Ewe Is Resistant to Disruption by Repeated, Acute Psychosocial Stress1

“…We have determined that psychosocial stress inhibits pulsatile LH secretion in ovariectomized sheep by reducing both gonadotropin-releasing hormone (GnRH) pulse amplitude [16] and pituitary responsiveness to GnRH [17]. Although the suppression of pulsatile GnRH secretion is independent of cortisol action [16], inhibition of pituitary responsiveness is caused by the concurrent rise in plasma cortisol [17].…”