Testosterone modulates growth hormone secretion at the hypothalamic hut not at the hypophyseal level in the adult male rhesus monkey

We investigated a possible modulation of growth hormone (GH) secretion by t estosterone by measuring the growth hormone releasing hormone (GHRH)-stimul ated and N-methyl-D,L-aspartic acid (NMA)-induced GH secretion in adult rhe sus monkeys. Intact, orchidectomized and testosterone-substituted (testoste rone enanthate 125 mg/ week, i.m. for 5 weeks) orchidectomized monkeys (n = 5) were used in the study. GHRH. (25 mu g/kg body weight) or NMA (15 mg/kg body weight) was infused through a Teflon cannula implanted in the sapheno us vein. Sequential blood samples were collected 30-60 min before and 60 mi n after the injection of the neurohormone or the drug at 10-20-min interval s. All bleedings were carried out under ketamine hydrochloride anaesthesia (initial dose 5 mg/kg body weight i.m., followed by 2.5 mg/kg at 30-min int ervals). The plasma concentrations of GH, testosterone and oestradiol (E-2) were determined by using specific assay systems. Administration of GHRH el icited a significant increase in GH secretion in all three groups of animal s. There was no significant difference in the responsiveness of pituitary s omatotrophs to exogenous GHRH challenges between intact and orchidectomized monkeys and testosterone replacement in orchidectomized animals did not si gnificantly alter the GHRH-induced GH response. The responsiveness of hypot halamic GHRH neurones apparently did undergo a qualitative change after orc hidectomy, as GH response to NMA was less in orchidectomized animals than i n intact monkeys. The responsiveness of GHRH neurones to exogenous NMA was restored and even potentiated when orchidectomized monkeys were treated wit h testosterone. Taken together, these findings suggest that testosterone do es not affect the sensitivity of the pituitary somatotrophs to GHRH but sti mulates the secretion of GH by modulation of the NMDA drive to GHRH neurone s.