GENE-EXPRESSION OF THE RECEPTOR FOR GROWTH-HORMONE-RELEASING HORMONE IS PHYSIOLOGICALLY REGULATED BY GLUCOCORTICOIDS AND ESTROGEN

We investigated the effects of glucocorticoids and estrogen on the gen e expression of growth hormone (GH) and the receptor for growth-hormon e-releasing hormone (GHRH) by measuring the mRNA levels of GH and GHRH receptor in pituitary tissues of Sprague-Dawley rats using Northern b lot hybridization and specific cDNA probes. Male rats, 6 weeks of age, were either adrenalectomized (or sham-operated) or treated with varyi ng doses of dexamethasone (40, 200, 500 or 1,000 mu g/kg/day, i.p.) fo r 3 days. Female rats, 4 weeks of age, were oophorectomized or sham-op erated, and treated with 17 beta-estradiol benzoate 25 mu g/kg/day (or vehicle) s.c. for 5 days starting 10 days after oophorectomy. Adrenal ectomy was associated with a reduction in weight gain and decreased GH RH receptor mRNA levels (p < 0.05 and p < 0.0001 versus sham-operated, respectively). Dexamethasone treatment, however, was associated with a dose-dependent reduction in weight gain (p < 0.0001) but dose-depend ent increases in GHRH receptor mRNA and GH mRNA levels (p < 0.0001 and p < 0.05, respectively). In the female rats, weight gain was increase d by oophorectomy (p < 0.005 vs. sham-operated) and decreased by estro gen treatment (p < 0.05 vs. vehicle-treated). Pituitary GHRH receptor mRNA levels were also increased by oophorectomy (p < 0.05) and decreas ed by estrogen (p < 0.005). GH mRNA levels were unchanged by oophorect omy but decreased after estrogen treatment (p < 0.05). In conclusion, our findings suggest that endogenous glucocorticoids and estrogen are physiological regulators of pituitary GHRH receptor gene expression. G lucocorticoids and estrogen also regulate GH secretion via effects on GH gene expression. Changes in GHRH receptor and GH mRNA levels cannot explain the growth retardation in dexamethasone-treated rats.