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Growth Dev Aging. 1990 Winter;54(4):165-71. Related Articles, Links
Melatonin increases serum growth hormone and insulin-like growth factor I (IGF-I) levels in male Syrian hamsters via hypothalamic neurotransmitters.
Vriend J, Sheppard MS, Borer KT.
Department of Anatomy, University of Manitoba, Winnipeg, Canada.
In male Syrian hamsters daily evening melatonin injections resulted in increased circulating levels of growth hormone (GH), as well as a modest increase in body weight. A substantial increase in serum levels of insulin-like growth factor I (IGF-I) was observed in all hamsters receiving evening injections of melatonin for 10 weeks. The melatonin-induced increase in serum IGF-I levels was interpreted as a result of increased release of GH during the 10 week period of melatonin administration. The increase in serum GH and IGF-I was associated with significantly decreased hypothalamic turnover of norepinephrine (NE). Since blocking NE synthesis with alpha methyl-p-tyrosine reduced serum GH, the melatonin-induced increase in GH could not readily be attributed to decreased NE turnover. Highly significant increases in 5-hydroxyindole acetic acid (5HIAA) concentrations and in ratios of 5HIAA to serotonin (5HT) were noted in extracts of hypothalamus and in extracts of brain stem, suggesting a serotonergic component to melatonin-induced increase in GH-induced IGF secretion and subsequent growth
Clin Endocrinol (Oxf). 1987 Apr;26(4):453-8. Related Articles, Links
Effect of oral administration of melatonin on GH responses to GRF 1-44 in normal subjects.
Valcavi R, Dieguez C, Azzarito C, Edwards CA, Dotti C, Page MD, Portioli I, Scanlon MF.
Sezione Endocrino Metabolica, Unita Sanitaria Locale, Reggio Emilia, Italy.
In order to investigate the role of melatonin on the neuroregulation of GH secretion, eight healthy male volunteers each underwent four separate tests in random order separated by at least 1 week. Following oral administration of melatonin (500 mg at -60 min and at -30 min) plasma GH levels were higher than after placebo at 45 min (mean +/- SEM 2.9 +/- 0.8 vs 0.9 +/- 0.4 ng/ml, P less than 0.01) and 60 min (mean +/- SEM 2.9 +/- 0.4 vs 0.8 +/- 0.1 ng/ml, P less than 0.05). Likewise, after prior administration of melatonin, GH responses to GRF 1-44 (1 micrograms/kg i.v. at 0 min) were greater than placebo plus GRF at 15 min (mean +/- SEM 22.4 +/- 6.1 ng/ml vs 11.3 +/- 2.3 ng/ml, P less than 0.05), 45 min (mean +/- SEM 26.2 +/- 5.3 ng/ml vs 13.3 +/- 2.5 ng/ml, P less than 0.01) and 60 min (mean +/- SEM, 24.7 +/- 7.4 ng/ml vs 11.1 +/- 2.5 ng/ml, P less than 0.05). In contrast we did not observe any effect of either 10(-9)M, 10(-7)M melatonin on in-vitro basal GH release and GH responses to 10(-8)M GRF by rat anterior pituitary cells in monolayer culture. These data suggest that melatonin plays a facilitatory role in the neuroregulation of GH secretion, probably by acting at the hypothalamic level.
Clin Endocrinol (Oxf). 1993 Aug;39(2):193-9. Related Articles, Links
Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone.
Valcavi R, Zini M, Maestroni GJ, Conti A, Portioli I.
2a Divisione di Medicina Interna, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
OBJECTIVE: There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release. DESIGN: The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 micrograms i.v. bolus). Study 2: GHRH (100 micrograms i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 micrograms i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 micrograms i.v. bolus) of GHRH. SUBJECTS: Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol. MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals. RESULTS: Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 micrograms) or submaximal (3 micrograms) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH. CONCLUSIONS: Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.
EUROPEAN JOURNAL OF ENDROCRINOLOGY, 1999, Vol 141, Iss 1, pp 22-26
2. Melatonin enhances exercise-induced GH secretion
There is evidence that melatonin may play a role in modulating pituitary secretion, although the mechanisms are unclear. Growth hormone (GH) is secreted by the pituitary gland, which is located on the lower part of the brain under the hypothalamus. The hypothalamus is a part of the brain involved in the functions of the autonomic nervous system, and in endocrine mechanisms, and it appears to play a role in neural mechanisms underlying moods and motivational states. This study examined the effects of a single dose of oral melatonin (5 mg) on exercise-induced GH secretion. Seven healthy males undertook an initial period of graded bicycle ergometric exercise to determine maximum workload and oxygen uptake (VO2max). They were subsequently studied on two further occasions, receiving either melatonin or placebo at the onset of each study. Bicycle exercise was performed for eight min at a workload corresponding to 70% of that achieved at VO2max. Serum GH and IGF-binding protein-1 (IGFBP-1) concentration was measured at 15-min intervals from the onset of the study until 120 min after exercise. Blood was also sampled for the measurement of blood glucose, insulin, non-esterified fatty acids, IGFBP-3, melatonin and vasopressin concentration. The results showed an exercise-induced increase in GH concentration following melatonin that was greater compared with placebo, as assessed by both area under the curve and peak increase in GH levels. The peak increase in IGFBP-1 levels after exercise was also significantly greater following melatonin compared with placebo but did not quite reach levels of significance as measured on a graph by area under the curve. Since exercise-induced GH secretion is thought to be caused indirectly through a hypothalamic pathway, it seems likely that melatonin facilitates GH secretion at a hypothalamic level.
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