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

• Published in: Biology of reproduction 1999, Vol.60 (1), p.164-168
• Main Authors: Adams, T.E, Sakurai, H, Adams, B.M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cortisol; Drug Interactions; estradiol; Estradiol - administration & dosage; Estradiol - blood; Estradiol - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; gonadotropin-releasing hormone; hormone receptors; Hormones and neuropeptides. Regulation; Hydrocortisone - administration & dosage; Hydrocortisone - blood; Hydrocortisone - pharmacology; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Kinetics; Male; messenger RNA; Orchiectomy; pituitary gland; Receptors, LHRH - genetics; Sheep - physiology; stress; Stress, Physiological - metabolism; temporal variation; Vertebrates: endocrinology; wethers
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod60.1.164

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 (E 2 ) 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) μg/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 μg E 2 /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 E 2 -dependent increase in GnRH receptor expression was assessed using wethers receiving E 2 (0.5 μg/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 E 2 delivery period. Stress-like 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 suppressive effect of C was transient, and tissue levels of GnRH receptor and receptor mRNA were comparable after 72 h of E 2 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.