MELATONIN STIMULATES GROWTH-HORMONE SECRETION THROUGH PATHWAYS OTHER THAN THE GROWTH HORMONE-RELEASING HORMONE

OBJECTIVE There is evidence that melatonin plays a role in the regulat ion of GH secretion. The aim of this study was to investigate the neur oendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH a dministration and compared the effects of melatonin with those of pyri dostigmine, a cholinergic agonist drug which is likely to suppress hyp othalamic somatostatin release. DESIGN The study consisted of four pro tocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 mu g i.v. bolus). Study 2: GHRH (100 mug i.v. bolus) or placebo were admi nistered at 0 minutes; oral melatonin or placebo were given at 60 minu tes and were followed by a second GHRH stimulus (100 mug i.v. bolus) a t 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridost igmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were a dministered on separate occasions. Study 4: placebo; oral melatonin (1 0 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostig mine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 mug i.v. bolus) of GHRH. SUBJECTS Four groups of eight normal male subjects, ages 22-35 years, were randomly assign ed to each protocol. MEASUREMENTS Growth hormone was measured by RIA a t 15-minute intervals. RESULTS Oral melatonin administration had a wea k stimulatory effect on GH basal levels. Prior melatonin administratio n approximately doubled the GH release induced by supramaximal (100 mu g) or submaximal (3 mug) doses of GHRH. Melatonin administration resto red the GH response to a second GHRH challenge, given 120 minutes afte r a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatoni n. However, the simultaneous administration of melatonin and pyridosti gmine was not followed by any further enhancement of GH release, eithe r in the absence or in the presence of exogenous GHRH. CONCLUSIONS Our data indicate that oral administration of melatonin to normal human m ales increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melat onin plays this facilitatory role at the hypothalamic level by inhibit ing endogenous somatostatin release, although with a lower potency tha n pyridostigmine. The physiological role of melatonin in GH neuroregul ation remains to be established.