M. Kellner et al., CORTICOTROPIN-RELEASING HORMONE INHIBITS MELATONIN SECRETION IN HEALTHY-VOLUNTEERS - A POTENTIAL LINK TO LOW-MELATONIN SYNDROME IN DEPRESSION, Neuroendocrinology, 65(4), 1997, pp. 284-290
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.