Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans

Abstract

An oral preparation of melatonin was administered daily at 22.00 h to 6 healthy volunteers during summer on 4 consecutive days (days 1\p=n-\4).The daily dose was 8 mg of melatonin as a single. Three 24-h melatonin, cortisol and prolactin profiles were determined in plasma by radioimmunological methods: 1) before treatment (day 0); 2) the first day after the 4-day treatment had been stopped (day 5), 3) the third day after withdrawal of this treatment (day 7). For the melatonin rhythm, an advanced phase was observed at day 7 vs day 0, whereas the amplitude and the mesor were not modified, whatever the day. For the prolactin profile, a significant increase as compared with the control day (day 0) was detected only at day 7 between 19.00 and 21.00 h. No modification was recorded for the plasma cortisol secretion.These results suggest that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion. This effect must be investigated over several days after the treatment has ended. The pineal gland, as an endogenous clock, plays a central role in the circadian and seasonal organiza¬ tion of biological rhythms in several species (Reiter 1981). Melatonin, the main indole compound syn¬ thesized by the pineal gland, presents a very marked circadian rhythmic secretion in humans and other species: plasma melatonin levels are high at night, during the scotophase, and low or undetectable during the light period. In humans, no clearly established role has been definitively at¬ tributed to melatonin: melatonin can induce sleep (Cramer et al. 1974; Vollrath et al. 1981), and modify mood and performance (Lieberman et al. 1984) or fatigue (Arendt et al. 1984). In all these studies, however, either the doses were supraphysiological or melatonin was given during day-time. Further, in adults, hormonal effects have been observed on plasma GH levels (Smythe & Lazarus 1974) or on GH and gonadotropin levels (Nordlund & Lerne 1977) during long-term treatment, on plasma pro¬ lactin and melatonin on the day following the last oral administration of a one-month treatment (Wright et al. 1986), and in children on plasma GH and prolactin levels after an acute injection of me¬ latonin (Lissoni et al. 1986). Moreover, Arendt et al. (1986) have shown that melatonin alleviates jet-lag, suggesting an interaction between this hormone and endogenous rhythms.We report here on the 24-h plasma melatonin, prolactin and cortisol profiles of 6 normal subjects studied on three occasions, the first before treat¬ ment (day 0), the second on day 1 (day 5) and the third on day 3 (day 7) after withdrawal of a 4-day melatonin course. This study was designed to evaluate the consequence of a semi-chronic treat¬ ment on the endocrine rhythms. Subjects and MethodsSix healthy young men (22-26 years of age) were en¬ rolled for this study which was developed within the scope of a research project on the effects of melatonin in

Melatonin and Human Chronobiology

“…The same study may have also influenced the first two investigations of the phase-shifting effects of melatonin in sighted people (Arendt et al 1985;Mallo et al 1988; for review, see Lewy and Sack 1997). Although we published a case report showing entrainment of a blind person to melatonin in the early 1990s (Sack et al 1990(Sack et al , 1991, it was not until the end of that decade that unequivocal entrainment (to 10 mg) could be demonstrated in a group of BFRs .…”

Melatonin and sleep in humans

“…On the basis of these results. the authors concluded that [Mallo et al, 1988;Wright et al, 1986;Waldhauser et al, 19871, thyroid releasing hormone [Paccotti et al, 19871, T3 or T4 [Wright et al, 19861, ACTH [Paccotti et al, 19871, growth hormone [Wright et al, 1986;Arendt et al, 1985;Waldhauseret al, 19871, luteinizing hormone [Lissoni et al, 1986;Arendt et al, 1985;Walhauser et al, 19871, FSH and TSH [Lissoni et al, 1986;Walhauser et al, 19871, or testosterone [Wright et al, 1986;Waldhauser et al, 19871. Despite the general lack of a demonstrated endocyine action, increased prolactin levels have been reported in pubertal, adolescent, and adult subjects following melatonin administration. Following administration of 0.1 mg/kg intravenous at 1500, prolactin production was significantly increased in pubertal [Mauri et al, 19851 and adolescent [Lissoni et al, 19861 subjects.…”

“…The majority of early studies that investigated the physiological effects of melatonin focused on its potenttal to modulate neuroendocrine systems. It was initially thought that the variability in the observed hypnotic effects of melatonin may be related to an indirect effect on a second neuroendocrine system [Lissoni et al, 1986;Mallo et al, 1988;Mauri et al, 1985;Waldhauser et al, 1987;Wright et al, 19861. However, studies have consistently shown few, if any, endocrine sequelae when melatonin is administered over a short period (i.e., 1 4 days). The majority of studies report no effect of melatonin on plasma levels of markers of pituitary or adrenal function [Paccotti et al, 19881, including cortisol ics of endogenous melatonin production and exogenous melatonin administration.…”

Melatonin Is Able to Influence Its Secretion in Humans: Description of a Phase-Response Curve

“…When several milligrams of melatonin, which produce supraphysiological plasma levels, are chronically or semichronically given per os in the late afternoon or evening, the melatonin rhythm is globally advanced, but its ampli tude remains very stable [1,2], Such data explain why melatonin is efficient in alleviating jet-lag syndrome when travelling from west to east [3,4], Recently, Lewy et al [5] described a melatonin phaseresponse curve (PRC) for the melatonin onset after oral administration of a low melatonin dose for 4 days. By this route of administration, however, the melatonin signal could display a heterogeneity from one subject to another, a consequence of the first-pass hepatic metabolism of the hormone.…”