Effect of Stress-Like Concentrations of Cortisol on Gonadotroph Function in Orchidectomized Sheep1

Abstract

The effect of stress-like concentrations of cortisol (C) on the feedback potency of estradiol (E2) was assessed using 32 orchidectomized sheep (wethers) assigned at random to 1 of 4 treatment groups in a 2 x 2 factorial design. Wethers received C (3. 6 mg/50 kg per hour; groups 2 and 4) or a comparable volume of C delivery vehicle (groups 1 and 3) as a continuous infusion for 7 days. During the final 48 h of infusion, wethers received E2 (0.3 microg/50 kg/h; groups 3 and 4) or E2 delivery vehicle (groups 1 and 2). The pattern of LH secretion was assessed during a 4-h period of intensive blood collection beginning 44 h after initiation of E2 infusion. Gonadotroph responsiveness (LH secretion induced by GnRH challenge [500 ng, i.v.]) was determined 48 h after E2 delivery was begun. Although the frequency of secretory episodes of LH was not affected (p > 0.05) by infusion of C or E2 alone, LH pulse frequency was significantly decreased in wethers receiving C and E2 in combination. In contrast, neither the magnitude of basal gonadotroph responsiveness nor the extent of E2-dependent augmentation of responsiveness was significantly affected by stress-like concentrations of C. In a second experiment, the effect of C on the magnitude of E2-induced increase in pituitary concentration of GnRH receptor and GnRH receptor mRNA was assessed using 32 additional wethers. Continuous infusion of E2 for 48 h increased (p < 0.05) tissue concentrations of GnRH receptor and GnRH receptor mRNA. Concurrent delivery of C did not affect (p > 0.05) E2-induced increase in GnRH receptor mRNA but significantly reduced the magnitude of the E2-dependent increase in pituitary concentration of GnRH receptor. Collectively, these data indicate that stress-like concentrations of C enhance the negative feedback potency of E2 and reduce estrogen-dependent augmentation of the concentration of GnRH receptor in pituitary tissue.

Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences

“…Nevertheless, their results also indicate that cortisol alone is not the major mediator of these effects. Infusion of cortisol alone into castrated rams for 7 days did not affect the frequency or amplitude of LH pulses, and pulse frequency was reduced only when oestradiol was also present (Daley et al, 1999). Furthermore, the suppression of the oestrogen-dependent increase in GnRH receptor gene expression by stress-like concentrations of cortisol was seen to be transient in nature .…”

“…In rams, an infusion of 2-4 mg cortisol min -1 for 9 h did not affect the LH response to GnRH (Fuquay and Moberg, 1983). However, the infusion of castrated rams with a combination of cortisol and oestradiol decreased the frequency of LH pulses (Daley et al, 1999). Infusion of oestradiol into castrated rams also increased the tissue concentrations of GnRH receptor and mRNA encoding GnRH receptor, and cortisol infusion reduced these responses Daley et al, 1999).…”

“…However, the infusion of castrated rams with a combination of cortisol and oestradiol decreased the frequency of LH pulses (Daley et al, 1999). Infusion of oestradiol into castrated rams also increased the tissue concentrations of GnRH receptor and mRNA encoding GnRH receptor, and cortisol infusion reduced these responses Daley et al, 1999). The authors of these studies concluded that cortisol is capable of enhancing the negative feedback effects of oestradiol and reducing the stimulation of GnRH receptor expression by oestrogen.…”

Influences of the stress endocrine system on the reproductive endocrine axis in sheep (Ovis aries)

“…Stress-like concentrations of cortisol (intravenous cannula delivery into left jugular vein at 3.6 mg/50 kg per hour continuous infusion for a period of 7) did not affect gonadotroph responsiveness or GnRH receptor and GnRH receptor mRNA in the pituitary of ovidectomised sheep, which was correlated with no significant change in GnRH secretion from the hypothalamus (Daley et al 1999b). Endotoxin injection significantly decreased the level of GnRH receptor mRNA by 80% in the anterior pituitary of anoestrous ewes, which was correlated with a decrease in LH secretion .…”

“…Tissue concentration of GnRH receptors in the anterior pituitary is considered to be a determinant of pituitary/gonadotroph responsiveness to GnRH (Daley et al 1999b). Stress-like concentrations of cortisol (intravenous cannula delivery into left jugular vein at 3.6 mg/50 kg per hour continuous infusion for a period of 7) did not affect gonadotroph responsiveness or GnRH receptor and GnRH receptor mRNA in the pituitary of ovidectomised sheep, which was correlated with no significant change in GnRH secretion from the hypothalamus (Daley et al 1999b).…”