CORTICOTROPIN-RELEASING HORMONE INHIBITS MELATONIN SECRETION IN HEALTHY-VOLUNTEERS - A POTENTIAL LINK TO LOW-MELATONIN SYNDROME IN DEPRESSION

Interactions between the hypothalamic-pituitary-adrenocortical (HPA) s ystem and melatonin secretion have been demonstrated, but only the eff ects of melatonin on the activity of the HPA system have been studied in man. Alterations of melatonin secretion described as low-melatonin syndrome have been demonstrated in patients suffering from a major dep ressive episode, and an inhibitory factor on melatonin secretion has b een postulated. We investigated whether corticotropin-releasing hormon e (CRH), which is thought to be involved in HPA abnormalities in depre ssed patients, can also suppress melatonin secretion in healthy volunt eers. Ten healthy male human volunteers in a double-blind study design received randomized hourly intravenous injections from 08.00 to 18.00 h that contained 10 mu g human CRH, 1 mu g adrenocorticotropic hormon e (ACTH), or placebo to simulate pulsatile hormone secretion. Plasma m elatonin and cortisol responses during the treatment and nocturnal sle ep electroencephalograms after the treatment were recorded. Administra tion of CRH reduced melatonin secretion significantly below values obt ained after administration of placebo and ACTH. Cortisol secretion was significantly enhanced by ACTH in comparison to both placebo and CRH. Electroencephalographic sleep parameters revealed no treatment effect s. Our findings suggest that CRH has an inhibitory effect on the pinea l secretion of melatonin in normal man. A mechanism via a release of c ortisol was not supported by our results. Secondary hormonal effects f rom changes in nocturnal sleep architecture were excluded. Further inv estigation of the action of CRH on melatonin secretion as well as the mutual feedback between the HPA system and the pineal gland may extend our knowledge of neuroendocrine alterations mediating the adaptive re sponse to stress and the eventual involvement in the pathogenesis of d epression.