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-dependent 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 infusion for 48 h. During the final 24 h of infusion, animals received concurrent infusion of estradiol (E2) at rates of 0 (groups 1 and 5), 0.5 (groups 2 and 6), 2.0 (groups 3 and 7), or 8.0 (groups 4 and 8) microg/50 kg per hour. Pituitary tissue was collected at the end of infusion. Although C did not affect (p > 0.05) the basal concentration of GnRH receptor or GnRH receptor mRNA, it reduced (p < 0.05) the increase in receptor and receptor mRNA induced by concurrent administration of 0. 5 microg E2/50 kg per hour. In contrast, the increase in GnRH receptor expression induced by higher levels of estrogen stimulation was not affected (p > 0.05) by concurrent administration of C. The effect of C on the temporal pattern of E2-dependent increase in GnRH receptor expression was assessed using wethers receiving E2 (0.5 microg/50 kg per hour) by continuous infusion for 0 (groups 1 and 5), 24 (groups 2 and 6), 48 (groups 3 and 7), or 72 h (groups 4 and 8). Animals received C (5.0 mg/50 kg per hour; groups 1-4) or vehicle (groups 5-8) beginning 24 h before, and continuing throughout, the E2 delivery period. Stress-like concentrations of C reduced (p < 0. 05) the increase in GnRH receptor and receptor mRNA induced after 24 h of E2 stimulation. However, the suppressive effect of C was transient, and tissue levels of GnRH receptor and receptor mRNA were comparable after 72 h of E2 infusion in animals receiving C or vehicle alone. Collectively these observations demonstrate that C suppresses estrogen-dependent increase in tissue concentrations of GnRH receptor and receptor mRNA. However, this effect of C is transient and not evident in animals receiving moderate to high levels of estrogen stimulation. This transient suppression of GnRH receptor expression may account, at least in part, for the anti-gonadal effect of glucocorticoids.
Adams
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Department of Animal Science, University of California, Davis, California 95616, USA. teadams@ucdavis.edu
Sakurai
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Adams
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D000818:Animals; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009919:Orchiectomy; D011966:Receptors, LHRH / Q000235:genetics*; D012756:Sheep / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism*
D011966:Receptors, LHRH; D004958:Estradiol; D006854:Hydrocortisone