Valcavi R, Zini M, Maestroni G J, Conti A, Portioli I
2a Divisione di Medicina Interna, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
Clin Endocrinol (Oxf). 1993 Aug;39(2):193-9. doi: 10.1111/j.1365-2265.1993.tb01773.x.
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.
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.
Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol.
Growth hormone was measured by RIA at 15-minute intervals.
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.
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.
有证据表明褪黑素在生长激素（GH）分泌的调节中起作用。本研究的目的是探讨褪黑素调节GH分泌的神经内分泌机制。因此，我们评估了口服褪黑素对给予生长激素释放激素（GHRH）后GH反应的影响，并将褪黑素的作用与吡啶斯的明（一种胆碱能激动剂药物，可能抑制下丘脑生长抑素释放）的作用进行了比较。
该研究包括在下午时段进行的四个方案。方案1：在静脉推注100微克GHRH前60分钟给予口服褪黑素（10毫克）或安慰剂。方案2：在0分钟时给予GHRH（100微克静脉推注）或安慰剂；在60分钟时给予口服褪黑素或安慰剂，并在120分钟时给予第二次GHRH刺激（100微克静脉推注）。方案3：分别给予安慰剂；口服褪黑素（10毫克）；口服吡啶斯的明（120毫克）；褪黑素（10毫克）加吡啶斯的明（120毫克）。方案4：在给予次最大剂量（3微克静脉推注）GHRH前60分钟，分别给予安慰剂；口服褪黑素（10毫克）；口服吡啶斯的明（120毫克）；褪黑素（10毫克）加吡啶斯的明（120毫克）。
四组年龄在22 - 35岁的正常男性受试者，每组八人，被随机分配到每个方案。
每隔15分钟通过放射免疫分析法测量生长激素。
口服褪黑素对GH基础水平有微弱的刺激作用。预先给予褪黑素使超最大剂量（100微克）或次最大剂量（3微克）GHRH诱导的GH释放增加约一倍。在首次静脉推注GHRH 120分钟后给予第二次GHRH刺激时，给予褪黑素可恢复GH反应。单独使用或在给予GHRH后使用吡啶斯的明的GH释放作用大于褪黑素。然而，无论是否存在外源性GHRH，同时给予褪黑素和吡啶斯的明均未使GH释放进一步增强。
我们的数据表明，对正常男性口服褪黑素通过与吡啶斯的明相同的途径增加基础GH释放和GH对GHRH的反应性。因此，褪黑素可能通过抑制内源性生长抑素释放在下丘脑水平发挥这种促进作用，尽管其效力低于吡啶斯的明。褪黑素在GH神经调节中的生理作用仍有待确定。
