Effect of stress-like concentrations of cortisol on estradiol-dependent expression of gonadotropin-releasing hormone receptor in orchidectomized sheep

The effect of stress-like concentrations of cortisol (C) on estrogen-depend ent expression of GnRH receptor was evaluated using orchidectomized sheep ( wethers; n = 6 animals per group). C (5.0 mg/50 kg per hour; groups 1-4) or a comparable volume of vehicle (groups 5-8) was delivered by continuous in fusion for 48 h. During the final 24 h of infusion, animals received concur rent infusion of estradiol (E-2) at rates of 0 (groups 1 and 5), 0.5 (group s 2 and 6), 2.0 (groups 3 and 7), or 8.0 (groups 4 and 8) mu g/50 kg per ho ur. Pituitary tissue was collected at the end of infusion. Although C did n ot affect (p > 0.05) the basal concentration of GnRH receptor or GnRH recep tor mRNA, it reduced (p < 0.05) the increase in receptor and receptor mRNA induced by concurrent administration of 0.5 mu g E-2/50 kg per hour. In con trast, the increase in GnRH receptor expression induced by higher levels of estrogen stimulation was not affected (p > 0.05) by concurrent administrat ion of C. The effect of C on the temporal pattern of E-2-dependent increase in GnRH receptor expression was assessed using wethers receiving E-2 (0.5 mu g/50 kg per hour) by continuous infusion for 0 (groups 1 and 5), 24 (gro ups 2 and 6), 48 (groups 3 and 7), or 72 h (groups 4 and 8). Animals receiv ed C (5.0 mg/50 kg per hour; groups lit) or vehicle (groups 5-8) beginning 24 h before, and continuing throughout, the E-2 delivery period. Stress-lik e concentrations of C reduced (p < 0.05) the increase in GnRH receptor and receptor mRNA induced after 24 h of E-2 stimulation. However, the suppressi ve effect of C was transient, and tissue levels of GnRH receptor and recept or mRNA were comparable after 72 h of E-2 infusion in animals receiving C o r vehicle alone. Collectively these observations demonstrate that C suppres ses estrogen-dependent increase in tissue concentrations of GnRH receptor a nd receptor mRNA. However, this effect of C is transient and not evident in animals receiving moderate to high levels of estrogen stimulation. This tr ansient suppression of GnRH receptor expression may account, at least in pa rt, for the anti-gonadal effect of glucocorticoids.