Melatonin Rise Research Articles

Influence of the photocycle and thermocycle on rhythms of plasma thyroxine and plasma and ocular melatonin in late metamorphic stages of the bullfrog tadpole, Rana catesbeiana

The diel fluctuations in plasma thyroxine (T 4) and plasma and ocular melatonin entrain to the light/dark (LD) cycle in the bullfrog tadpole, although the phase of the rhythms changes during development. Previous studies on the rhythmicity of these hormones were conducted under various LD cycles, but with a constant temperature, raising the question of the role of the natural thermocycle in determining the phase of the rhythms, and the changes that occur in the hormone levels and rhythms during late metamorphosis. To study this question, tadpoles were acclimated to simulated natural conditions of 14.5L:9.5D with a corresponding thermocycle in which the thermophase was 28 °C and the cryophase was 18 °C, or to the same thermocycle under constant light (24L). On both photoregimens, the diel fluctuations changed between prometamorphosis and metamorphic climax. However, more statistically significant rhythms, as indicated by the cosinor, occurred on 14.5L:9.5D than on 24L. At climax on the LD cycle, all hormones peaked around the same time in the late scotocryophase, whereas on 24L, plasma T 4 peaked in the thermophase and plasma and ocular melatonin peaks occurred some distance from each other early in the cryophase. The earlier peaks of plasma and ocular melatonin on 24L were due to a transient rise in these hormones at the onset of the cryophase, which was not sustained in the absence of an LD cycle. On 14.5L:9.5D with a corresponding thermocycle, the hormone rhythms had nearly the same phases as was found in previous work on 12L:12D at a constant temperature of 22 °C, allowing for minor phase shifting due to the photocycle differences, indicating that in this species laboratory studies on constant temperature give valid results even in the absence of a thermocycle. The findings show that the phases of the hormone rhythms are determined by the LD cycle although the onset of the cryophase, in the absence of a photocycle, may exert some influence on the nighttime rise in melatonin. The developmental rise in plasma T 4, and drop in plasma melatonin, occurred on both 14.5L:9.5D and 24L, indicating, taken together with previous work, that these climactic changes were independent of temperature and light cycling.

Effect of photoperiod manipulation on the daily rhythms of melatonin and reproductive hormones in caged European sea bass ( Dicentrarchus labrax)

Reproduction in fish is cyclical and timed to guarantee the survival of the offspring. Seasonal variations in reproductive hormones of fish have been deeply investigated in fish over the last years. However, there are few studies regarding the daily changes in reproductive hormone profiles in teleosts. The aim of the present research was to investigate the effects of photoperiod manipulation on melatonin and reproductive hormones (pituitary sbGnRH, pituitary LH and plasma LH, testosterone [T], and 11-ketotestosterone [11KT]) daily rhythms in male sea bass, kept in net cages under farming conditions in winter (9L:15D). Fish were distributed in two groups, one under constant long photoperiod (18L:6D) and the other under natural photoperiod. The photoperiod strongly influenced the daily melatonin profile, so that the duration of the nocturnal melatonin rise was longer in the control group than in the group exposed to the artificial photoperiod (18L:6D). A daily rhythm was observed in the pituitary sbGnRH profile in both groups, showing the lowest levels during the dark period. A daily rhythm of pituitary LH was detected in the control group, which was suppressed in the group under long photoperiod. Daily variations in plasma LH were observed, the highest levels being found in the dark phase in both groups, although this profile was significantly altered by artificial light, maintaining a fixed relationship between the first nocturnal rise of melatonin and the nocturnal peaks of plasma LH in both groups. Plasma T levels showed significant fluctuations in their daily cycle following a sinusoidal pattern with an acrophase around sunrise in both groups, without any influence of light regime. No significant daily variations in plasma levels of 11-KT were observed in none of the groups. Our results provide the first evidence of the presence of daily variations in pituitary sbGnRH content, pituitary and plasma LH, and plasma T in sea bass. Artificial lights suppressed the circulating melatonin and significantly affected the daily rhythm of LH storage and release.

Abnormal nocturnal melatonin secretion and disordered sleep in abstinent alcoholics

BackgroundAlcoholic patients show prominent disturbance of sleep as measured by electroencephalogram, with difficulties in the onset and maintenance of sleep. Given the role of melatonin in the regulation of the sleep–wake cycle, this study examined the relationship between nocturnal expression of melatonin and sleep in alcoholics as compared with control subjects. MethodsAlcoholic patients (n = 11) and comparison control subjects (n = 10) underwent all-night polysomnography and serial blood sampling every 30 min from 10:00 pm to 6:30 am for measurement of circulating levels of melatonin and cortisol. ResultsCoupled with prolonged sleep latency, alcoholics showed lower levels of melatonin during the early part of the night and a delay in the onset of the nocturnal plateau or peak value of melatonin as compared with control subjects. The nocturnal delay of melatonin correlated with prolonged sleep latency. Circulating levels of cortisol were lower during the early part of the night and higher in the late part of night in the alcoholics as compared with the control subjects. ConclusionsA delay in the nocturnal rise of melatonin may contribute to disordered sleep in chronic alcoholics, with implications for the use of melatonin in the treatment of insomnia in recovering alcoholics.

Melatonin in rat milk and the likelihood of its role in postnatal maternal entrainment of rhythms.

The rhythm of melatonin in rat milk and the capacity of pups to synthesize and metabolize melatonin were studied. Melatonin was undetectable in milk in the light (< 21 pM), but increased rapidly 2-4 h after dark to peak at 357 +/- 66 pM at mid-dark. Oral or subcutaneous administration of melatonin to 5- and 10-day-old pups resulted in peak plasma melatonin levels 30 min after administration and rapid metabolism. Increases in pineal and plasma melatonin levels at night were detected at 5 and 6 days of age, respectively. Isoproterenol administration (2 microg/g body wt) at mid-light to day 10 pups increased plasma melatonin from 312 +/- 40 pM to 1,298 +/- 160 pM, whereas propranolol (2 microg/g body wt) suppressed nocturnal melatonin secretion from 1,270 +/- 128 pM to 395 +/- 66 pM. The rise of pineal and plasma melatonin in day 10 pups occurred 1 and 2 h after dark onset, respectively, preceding the onset in dams by 3 and 4 h, respectively. Propranolol administration to 2- and 5-day lactating dams inhibited plasma and milk melatonin at night but had no effect on their suckling pups. Transfer of melatonin via the milk is unlikely to provide an entraining signal for rat pups.

Photoperiod, Reproduction, and Immunity in Select Strains of Inbred Mice

The purpose of this study was to determine whether decreased day lengths affect reproduction or the immune system in inbred mice. Irrespective of a nocturnal pineal melatonin rise, the signal for day length information, body and testis weights were the same in various strains 8 weeks after transfer from long to short days (16 to 8 h of light/day) compared to mice that remained in long days. Serum testosterone was unaffected by the photoperiod shift. The second goal was to determine whether the shift from long to short days influenced lymphocyte populations in spleen or blood, as well as innate and cell-mediated immune cell functions in C3H/HeN mice, an inbred strain with a robust melatonin rhythm. By flow cytometry, a stable percentage and number of B cells, T cells, and natural killer cells were identified in spleen from mice in both long and short days during the day and night. This complement of immunophenotypes in spleen suggests that equivalent functional capabilities persist in secondary lymphoid tissue of mice irrespective of day length. This was supported by findings that cytolytic activity by splenic natural killer cells (innate immunity) and antigen-induced T cell-dependent B cell antibody production (adaptive immunity) were similar in mice in long and short days. In blood, cell numbers but not helper T cell subset percentages (i.e., naive, memory, cytotoxic, or activated) were augmented in mice in short compared to long days, a consequence of increased circulating B cells. Day length differences in certain immunophenotypes in circulation may forecast photoperiod-mediated alterations in responsiveness to pathogens that are associated with a change in season. At night, the reduced proportion of cytotoxic T cells (long and short days), as well as increases in the percentage of activated T cells (long days), B cells (short days), and NK cell activity (long and short days) relative to daytime, suggests that surveillance and function by select immunophenotypes may adapt to circadian transitions even in highly inbred species. Thus, inbred mice retain capabilities for photoperiod to influence trait-specific aspects of immune cell but not reproductive function.

Paraventricular–subparaventricular hypothalamic lesions selectively affect circadian function

The circadian timing system has three principal components: (i) entrainment pathways, (ii) pacemakers, and (iii) efferent pathways from the pacemakers that convey the circadian signal to effector systems. The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal mammalian circadian pacemaker and, although we understand the organization of entrainment pathways to the SCN and the pacemaker itself, we know much less about the functional organization of SCN projections mediating control of effector systems. It is unclear, for example, whether specific subsets of SCN projections control specific effector systems. In this study, we analyzed the effects of lesions ablating the paraventricular hypothalamic nucleus (PVH), with variable extension into the subparaventricular zone (SPVZ) and adjacent structures, on nocturnal pineal melatonin production and rhythms in core body temperature (Tb) and rest–activity (R–A). In accordance with prior work, ablation of the PVH abolishes the nocturnal rise in pineal melatonin. Lesions restricted to the PVH do not affect rhythms in Tb and R–A but lesions extending caudally and ventrally into the SPVZ disrupt the R–A rhythm proportionate to the interruption of caudal SCN projections without affecting the rhythm in Tb. We conclude that pacemaker regulation of the circadian rhythms analyzed in this study is mediated by discrete sets of SCN projections: (i) dorsal projections to the PVH control pineal melatonin production; (ii) rostral projections to the anterior hypothalamic/preoptic areas mediate the Tb rhythm; and (iii) caudal projections to the SPVZ and hypothalamic arousal systems located in the posterior and lateral hypothalamic areas control the rhythm in R–A.

Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women.

Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the normal nocturnal rise in melatonin. This 1994-1996 Washington State study investigated whether such exposure was associated with lower nocturnal urinary concentration of 6-sulfatoxymelatonin in 203 women aged 20-74 years with no history of breast cancer. Each woman was interviewed and provided data on the following for a 72-hour period at two different seasons of the year: 1) magnetic field and ambient light measured every 30 seconds in her bedroom, 2) personal magnetic field measured at 30-second intervals, and 3) complete nighttime urine samples on three consecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin level was associated with more hours of daylight, older age, higher body mass index, current alcohol consumption, and current use of medications classified as beta blockers, calcium channel blockers, or psychotropics. After adjustment for these factors, higher bedroom magnetic field level was associated with significantly lower urinary concentration of 6-sulfatoxymelatonin during the same night, primarily in women who used these medications and during times of the year with the fewest hours of darkness. These results suggest that exposure to nighttime residential 60-Hz magnetic fields can depress the normal nocturnal rise in melatonin.

Melatonin rhythms in European sea bass plasma and eye: influence of seasonal photoperiod and water temperature.

The transduction of seasonal information from the environment (i.e., photoperiod and water temperature) into melatonin rhythms was studied in sea bass. Plasma and ocular melatonin (N-acetyl-5-methoxytryptamine) was determined in autumn, winter, spring and summer (experiment 1) under natural culture conditions, and in the summer and winter solstices under both natural and "6-month out-of-phase" photoperiods (experiment 2). At each sampling, 48 sea bass were sacrificed at a rate of 6 fish every 3 hr and the level of melatonin was determined in plasma and eye cup samples by ELISA. In experiment 1, significant diel changes were observed in plasma melatonin, with nocturnal melatonin varying from 144 pg/mL (summer) to 23 pg/mL (autumn), while diurnal melatonin remained low, around 8 pg/mL throughout the year. In experiment 2, the photoperiod length was shown to control the duration of the nocturnal melatonin rise, while the water temperature determined the amplitude of the melatonin rhythm. Ocular melatonin peaked during daytime in autumn and winter, but no significant changes were detected in summer and spring. In conclusion, plasma melatonin rhythms in sea bass reflect the pineal capacity to integrate seasonal information and supply precise calendar information, which may synchronize different physiological processes such as annual reproduction and feeding rhythms.

Aging, reproduction, and the melatonin rhythm in the Siberian hamster.

The present study tested the hypothesis that responsiveness to melatonin, the presence of the melatonin rhythm in circulation, and parameters of the GnRH neuron system are sustained across the aging continuum in Siberian hamsters. Afternoon melatonin injections induced testicular atrophy in 42% of aged males compared with 100% of adult males. The proportion of aged males failing to respond to the melatonin injections was similar to the proportion that failed to undergo testicular regression upon exposure to short days. Exposure to short days induced testicular atrophy in juvenile and adult hamsters; however, regression was incomplete or absent in 43% of aged males. The nocturnal rise in melatonin was similar with regard to duration and peak amplitude, and appropriate with respect to photoperiod in 25-day-old juveniles, adult (5 months), and aged (17 months) hamsters. Neither advanced age nor timed melatonin treatments affected GnRH neuron numbers or distribution. Fertility was maintained in aged and adult males to a comparable extent with respect to latency to first litter and number of pups per litter; reproductive success was dramatically reduced in aged compared with adult females. Because melatonin rhythms accurately reflect day length information throughout the continuum from puberty to advanced age, the present evidence suggests that limitations in testis regression in response to short days or exogenous melatonin in a subset of aged males result from a reduced ability to respond to melatonin. In the wild, failure to undergo testicular regression in the presence of shortening day lengths may extend the breeding season of aged males.

The decrease in plasma melatonin at metamorphic climax in Rana catesbeiana (bullfrog) tadpoles is induced by thyroxine

Melatonin decreases in the plasma of Rana catesbeiana (bullfrog) tadpoles at the climax of metamorphosis when the thyroxine (T 4) level peaks. Since melatonin inhibited thyroid function in vitro, it would be of interest to determine if the decline in plasma melatonin permits greater thyroid hormone secretion, or if the increasing levels of T 4 cause the climactic decrease in plasma melatonin. The reciprocal effects of administering T 4 or melatonin just prior to metamorphic climax were examined in tadpoles kept at 22°C on an 18L:6D cycle. If melatonin functions as a thyroid antagonist at later metamorphic stages, administration of melatonin should decrease plasma T 4, whereas if T 4 causes the decline in plasma melatonin, T 4 treatment of tadpoles prior to climax should induce the climactic melatonin decrease prematurely. Once daily injection of 40 μg melatonin for 5 days at 19.30 h had no effect on metamorphic progress, or on plasma T 4 or melatonin levels, except for a transient rise in melatonin just after the injection. Immersion in 2.2×10 −4 M melatonin for 6 days accelerated metamorphosis and decreased plasma melatonin, but had no effect on plasma T 4. Administration of T 4 by injection of 0.2 μg, or immersion in a 6.3×10 −8 M solution accelerated metamorphosis more than melatonin immersion, raised plasma T 4 to climax levels, and induced a decrease in plasma melatonin. We conclude that rapid clearance of exogenous melatonin from the circulation in these experiments did not allow it to affect plasma T 4, and that there is clear evidence that the rise in T 4 induces the climax decrease in plasma melatonin. The finding that immersion in a high level of melatonin can lower plasma melatonin and accelerate metamorphosis, whereas a single daily injection does not, provides an explanation for some of the contradictory reports in the literature concerning melatonin's effect on tadpole metamorphic progress.

Effects of Halothane, Pentobarbital and Ketamine on Serum Melatonin Levels in the Early Scotophase in New Zealand White Rabbits

In mammals, the nocturnal rise in pineal melatonin is regulated by signals from the endogenous clock, the hypothalamic suprachiasmatic nuclei. There have been few reports on whether anaesthetics which modulate multisynaptic neuronal functions affect melatonin secretion. We studied the effects of three commonly used anaesthetics, halothane, pentobarbital and ketamine, on serum melatonin levels in male New Zealand white rabbits. Seven blood samples were collected, 30–60 min apart, before, during and after anaesthesia. Experiments were performed in the late light and early dark period, so that changes in melatonin secretion would be reflected in the onset and/or level of nocturnal serum melatonin. Serum melatonin levels were determined by radioimmunoassay. Our results indicated that halothane attenuated the release of melatonin and pentobarbital had no apparent effect, whereas ketamine potentiated the release of melatonin. These findings suggest that melatonin levels may be affected in patients anaesthetized with halothane or ketamine, resulting in disturbed biological rhythms, especially the sleep-wake cycle following recovery.

The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats.

We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations, 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light: dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures, an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Px), multiplicity (2.18 tumors/tumor-bearing NMU control, 1.89 NMU + light, 2.39 NMU + Px), or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Px). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland.

Effect of long-term pinealectomy on growth and precocious maturationin Atlantic salmon, Salmo salar parr

While the pineal organ in poikilothermic vertebrates consistently influences a number of physiological processes, its precise role, and what controlling signal (hormonal and/or neural) is abolished by its removal, is still uncertain. For this reason, the effect of long-term pinealectomy (PINX) on seasonal growth and reproductive development was investigated in Atlantic salmon, Salmo salar, parr. Mean daytime plasma melatonin level in the control, sham-operated and PINX fish was 35 pg·mL –1 in all groups, while mean night-time levels were 296, 255 and 25 pg·mL –1, respectively, indicating that PINX abolished the natural nocturnal rise in melatonin. Pinealectomy did not influence the incidence or timing of early sexual maturation in the male parr. However, pinealectomy significantly affected growth, its effect being strongly seasonally dependent. Compared to sham-operated and control fish, pinealectomized fish showed significantly lower specific growth rates (SGRs) during the period of lengthening photoperiod up until the summer solstice. Thereafter, corresponding to the season of decreasing photoperiods, the pinealectomized fish exhibited higher SGRs. These results suggest a functional relationship between the pineal organ and somatic growth in the Atlantic salmon, although what controlling signal from the pineal (melatonin or neural) is involved has yet to be determined.

Regulation of emotional behaviour by day length in mice: implication of melatonin.

Pineal melatonin secretion occurs at night in all vertebrates and the duration of its secretion is negatively correlated with day length. As short-day exposure was previously shown to decrease emotional behaviour of mice toward an unfamiliar environment, the present study was designed to determine whether such behavioural changes could be mediated by melatonin. In a first experiment, the effects of a 3-week exposure to various day lengths (18h-6h, 12h-12h and 6h-18h light-dark conditions) on neophobic behaviour (free-exploratory paradigm) were examined in both BALB/c mice, which exhibit a very transitory melatonin peak of low amplitude in a 12h light-12h dark cycle, and C3H/He mice, which present a clear melatonin rise during the night-time. A second experiment was designed to determine if the decrease of emotional reactivity induced by a short-day exposure (6h-18h light-dark cycle during 3 weeks) in C3H/He mice could be counteracted by a daily treatment with a melatonin antagonist, S 22153 (1, 5 and 25 mg/kg/day). The short-day exposure was found to decrease neophobic reactions in both C3H/He and BALB/c mice. In contrast, the long-day exposure enhanced neophobia in C3H/He mice only. S 22153 was found to counteract, in a dose-dependent manner, the anxiolytic-like effects induced by the short-day exposure in C3H/He mice. The present results provide evidence that the modulation of circulating melatonin could be involved in the emotional changes related to day-length variations. Further studies are needed to investigate whether pinealectomy could counteract the photoperiod-related changes in anxiety.

Serum concentrations of melatonin during scotophase and photophase in 3, 4, 5 and 6 months old gilts and barrows.

One-hundred-twenty prepubertal crossbred gilts (Hampshire x Duroc) x (Yorkshire x Landrace) were removed from the nursery at 68.7+/-0.4 days of age and 23.6+/-0.9 kg body weight and relocated to a conventional grower-finisher unit. In addition, 60 barrows of similar genetics were relocated from the nursery at 71.0+/-0.5 days of age and 27.4+/-0.5 kg body weight to the same building. Twelve mature anestrous ewes that weighed 77.0+/-2.4 kg were assigned randomly to one of four pens of equal dimensions among the pens containing pigs. Ewes were included in this study to serve as positive controls since their secretory profiles of melatonin are well characterized. All pigs were bled by jugular venipuncture at approximately 3, 4, 5 and 6 months of age. At each age in the pigs and the mature ewes, a single sample was obtained during photophase and scotophase. Illumination intensity during the period of incandescent lighting averaged 220 1x. Blood collection was initiated approximately 4 h after sunrise and 3.5-4 h after sunset. The proportion of animals that exhibited a nocturnal rise in melatonin (MEL) was similar (P > 0.05) between gilts and barrows, but was higher (P < 0.002) in ewes than in pigs at each age examined. A greater proportion (P = 0.007) of 3 month old barrows had a nocturnal rise of MEL than any other age of barrow. Similarly, there was a tendency (P = 0.06) for more 3 month old gilts to exhibit a nocturnal increase in serum MEL than 4, 5 or 6 month old gilts.

Behavioral and neuroendocrine characteristics of the night-eating syndrome.

Investigators first described the night-eating syndrome (NES), which consists of morning anorexia, evening hyperphagia, and insomnia, in 1955, but, to our knowledge, this syndrome has never been subjected to careful clinical study. To characterize NES on the basis of behavioral characteristics and neuroendocrine data. A behavioral observational study was conducted between January 1996 and June 1997 in a weight and eating disorders program at the University of Pennsylvania. A neuroendocrine study was conducted from May through August 1997 at the Clinical Research Center of the University Hospital, Tromso, Norway. The behavioral study included 10 obese subjects who met criteria for NES and 10 matched control subjects. The neuroendocrine study included 12 night eaters and 21 control subjects. Behavioral study subjects were observed for 1 week on an outpatient basis, and neuroendocrine study subjects were observed during a 24-hour period in the hospital. The behavioral study measured timing of energy intake, mood level, and sleep disturbances. The neuroendocrine study measured circadian levels of plasma melatonin, leptin, and cortisol. In the behavioral study, compared with control subjects, night eaters had more eating episodes in the 24 hours (mean [SD], 9.3 [0.6] vs 4.2 [0.2]; P<.001) and consumed significantly more of their daily energy intake at night than did control subjects (56% vs 15%; P<.001). They averaged 3.6 (0.9) awakenings per night compared with 0.3 (0.3) by controls (P<.001). In night eaters, 52% of these awakenings were associated with food intake, with a mean intake per ingestion of 1134 (1197) kJ. None of the controls ate during their awakenings. In the neuroendocrine study, compared with control subjects, night eaters had attenuation of the nocturnal rise in plasma melatonin and leptin levels (P<.001 for both) and higher circadian levels of plasma cortisol (P = .001). A coherent pattern of behavioral and neuroendocrine characteristics was found in subjects with NES.

Evidence against alpha2-adrenoceptor involvement in the regulation of rat melatonin synthesis by ambient lighting

This study was carried out to clarify the role of α 2-adrenoceptors in the regulation of pineal melatonin synthesis. Medetomidine, a selective α 2-adrenoceptor agonist, was previously found to be a potent suppressor of nocturnal melatonin levels in rats. Medetomidine and α 2-adrenoceptor antagonists atipamezole and yohimbine were injected into rats in different conditions, and their pineal melatonin contents were measured by radioimmunoassay. Experiment 1: Blocking the α 2-adrenoceptors and possible non-adrenergic binding sites with atipamezole did not counteract the light-induced suppression of nocturnal melatonin. These receptors are, thus, not essential for the suppression of melatonin by light. Experiment 2: Blocking the α 2-adrenoceptors with atipamezole or yohimbine did not sensitize the pineal melatonin synthesis to daytime darkness in the light/dark-entrained rats. The binding sites are not involved in keeping the daytime melatonin levels low, even in darkness. Experiment 3: The rats were sensitized to daytime darkness by keeping them for seven days in constant light. The dark-elicited melatonin rise was suppressed by a lower dose of medetomidine than the normal nocturnal rise in light/dark-entrained rats, while atipamezole had no effect. The results showed that α 2-adrenoceptor insufficiency is not involved in the constant light-induced pineal supersensitivity. In summary, the experiments indicated that the physiological regulation of melatonin synthesis by ambient lighting in rats does not depend on α 2-adrenergic mechanisms.

Adjustment of the human melatonin and cortisol rhythms to shortening of the natural summer photoperiod

Fifteen human subjects were exposed to natural outdoor summer light from 0415 h until 2000 h for 4 days and then from 0800 h until 1600 h for another 4 days. Following shortening of the natural summer photoperiod, times of the morning salivary melatonin decline and cortisol rise did not change whereas the time of the evening melatonin rise phase advanced by about 1.5 h within 1 day and further did not change significantly. Consequently, the melatonin signal duration extended markedly within 1 day. The data show that the compressed melatonin rhythm waveform in humans experiencing a long natural summer photoperiod from sunrise until sunset may change rapidly following a shortening of the photoperiod.

Chronic exposure to 2.9 mT, 40 Hz magnetic field reduces melatonin concentrations in humans.

Diurnal rhythm of serum melatonin concentrations was estimated in 12 men with low back pain syndrome before and after exposure to a very low-frequency magnetic field (2.9 mT, 40 Hz, square wave, bipolar). Patients were exposed to the magnetic field for 3 weeks (20 min per day, 5 days per week) either in the morning (at 10:00 hr) or in the late afternoon (at 18:00 hr). Significant depression in nocturnal melatonin rise was observed regardless of the time of exposure. This phenomenon was characteristic for all the subjects, although the percent of inhibition of melatonin secretion varied among the studied individuals.

Diurnal Rhythm of Melatonin in Bovine Milk: Pharmacokinetics of Exogenous Melatonin in Lactating Cows and Goats

We investigated whether the melatonin levels in bovine milk exhibit a similar daily rhythm as serum levels. In 4 Ayrshire cows at the beginning of the lactation period in May the nocturnal rise in milk melatonin was moderate (from 7 +/- 2 pg/ml at noon to 15 +/- 1 pg/ml at night; mean +/- SEM) and did not correlate well with the melatonin level in serum (from 7 +/- 2 pg/ml to 27 +/- 7 pg/ml, respectively). On the other hand, 6 cows in a later phase of lactation, studied in February, showed a clear long-lasting nocturnal melatonin increase both in serum (from 9 +/- 1 pg/ml at noon to 26 +/- 3 pg/ml at night) and in milk (from 12 +/- 5 pg/ml to 26 +/- 7 pg/ml, respectively). Melatonin kinetics during lactation was studied in more detail in 4 Ayrshire cows and 4 dairy goats by giving an intravenous bolus injection of melatonin. A 3-compartment model with melatonin elimination from the central compartment was used to describe the data. The values (mean +/- SD) for the cows and the goats were: elimination half-life 27 +/- 4 min and 27 +/- 1 min, mean residence time 24 +/- 4 min and 18 +/- 4 min, steady state distribution volume 1.0 +/- 0.3 l/kg and 0.6 +/- 0.1 1/kg (p < 0.05), and plasma clearance 0.044 +/- 0.004 l/kg/min and 0.035 +/- 0.011 l/kg/min, respectively. Following injection, the melatonin concentration in milk increased rapidly and exceeded the corresponding serum value 15-30 min later, remaining thereafter above the serum level. Our results suggest that milk melatonin levels reflect blood concentrations of melatonin with a short delay.