Suppression of human growth hormone secretion by melatonin and cyproheptadine

Pituitary growth hormone (GH) release in the rat is stimulated via serotoninergic pathways and can be inhibited by treatment with compounds that act as serotonin antagonists, such as cyproheptadine or the pineal gland hormone, melatonin. To investigate a possible role for serotonin in the control of human GH release, the effects of cyproheptadine and melatonin administration on the GH responses of normal male subjects were examined. The oral administration of cyproheptadine (8-12 mg daily for 5 days) to normal subjects reduced their GH responses to both insulin-induced hypoglycemia and physical exercise to a highly significant extent. Similarly, the mean GH responses of 10 subjects to insulin-induced hypoglycemia were significantly reduced after the prior oral administration of melatonin (1 g). The data presented show that serotonin antagonism has a similar effect on GH secretion in man to that observed in the rat and provides further evidence for serotoninergic, and possibly pineal, involvement in the control of human GH secretion.