L. 5-a androstane diol stimulates the pituitary growth hormone responsiveness to growth hormone releasing hormone more effectively than testosterone or dihydrotestosterone in rats. Acta Endocrinol 1992;126:162-6. ISSN 0001-5598 The effect of different androgens and estradiol on pituitary responsiveness to growth hormone releasing hormone was studied in intact and orchidectomized adult male Wistar rats, by injecting subcutaneously immediately after orchidectomy for two weeks with testosterone, dihydrotestosterone, 5-\g=a\ androstane, 3-\g=a\,17 \g=b\-diol or estradiol dissolved in olive oil (in doses of 0.2 or 2.0 mg\m=.\kg-1 \m=.\day-1) or vehicle. Pituitary responsiveness was tested in pentobarbital anaesthetized rats by measuring growth hormone plasma levels at different times after administration of growth hormone releasing hormone (1-29) NH2. We found that: (a) High doses of testosterone, dihydrotestosterone and 5-\g=a\androstane, 3-\g=a\,17 \g=b\-diol restored gonadotropin plasma concentrations and organ weights altered by orchidectomy; (b) both pituitary growth hormone content and concentration remained unaffected after orchidectomy or androgen replacement and decreased significantly after estradiol injection; (c) orchidectomy significantly reduced growth hormone-stimulated growth hormone releasing hormone secretion; (d) treatment with 5-\g=a\androstane, 3-\g=a\, 17 \g=b\-diol increased more than testosterone or dihydrotestosterone both the peak concentration and the mean growth hormone secretion after growth hormone releasing hormone stimulation: (e) no differences were observed in the treatment with testosterone or dihydrotestosterone; (f) estradiol given at a dose of 0.2 mg\m=.\kg-1\m=.\day-1 increased pituitary responsiveness to growth hormone releasing hormone. These results demonstrated that testosterone and 5-\g=a\androstane, 3-\g=a\, 17 \g=b\-diol, which do not differ in their action on pituitary growth hormone content, increased the pituitary responsiveness to growth hormone releasing hormone differently and that the low pituitary responsiveness to growth hormone releasing hormone previously described in prepubertal animals was not due mainly to the secretion of 5-\g=a\androstane, 3-\g=a\,17 \g=b\-diol.Pituitary secretion of GH in response to GHRH increased with age (1-5) and after testosterone treatment (2). However, the role of the testis in the control of GHRHinduced GH release is controversial and we have recently described (4) how the increase in pituitary responsive¬ ness to GHRH with age is independent of the testis and occurs in orchidectomized animals. The effect of orchi¬ dectomy depended on the age of the rats and on the time elapsed after orchidectomy, since an increase in pituitary responsiveness to GHRH was observed a week after orchidectomy in prepubertal animals, whereas in adult males orchidectomy decreased the effectiveness of GHRH. Since the prepubertal testis secretes mainly 5-a androstane, 3-a, 17 /?-diol (a-diol) (6, 7), we suggested that this steroid, unlike testosterone, may...