We investigated the effects of glucocorticoids and estrogen on the gene expression of growth hormone (GH) and the receptor for growth-hormone-releasing hormone (GHRH) by measuring the mRNA levels of GH and GHRH receptor in pituitary tissues of Sprague-Dawley rats using Northern blot hybridization and specific cDNA probes. Male rats, 6 weeks of age, were either adrenalectomized (or sham-operated) or treated with varying doses of dexamethasone (40, 200, 500 or 1,000 µg/kg/day, i.p.) for 3 days. Female rats, 4 weeks of age, were oophorectomized or sham-operated, and treated with 17β-estradiol benzoate 25 µg/kg/day (or vehicle) s.c. for 5 days starting 10 days after oophorectomy. Adrenalectomy was associated with a reduction in weight gain and decreased GHRH 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-dependent increases in GHRH receptor mRNA and GH mRNA levels (p < 0.0001 and p < 0.05, respectively). In the female rats, weight gain was increased by oophorectomy (p < 0.005 vs. sham-operated) and decreased by estrogen treatment (p < 0.05 vs. vehicle-treated). Pituitary GHRH receptor mRNA levels were also increased by oophorectomy (p < 0.05) and decreased by estrogen (p < 0.005). GH mRNA levels were unchanged by oophorectomy 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. Glucocorticoids 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 ra