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Spontaneous central melatonin secretion and resorption kinetics of exogenous melatonin: a ventricular CSF study.

Pineal secretion of melatonin, a potential sleep-inducing agent, is stimulated by nighttime darkness. To gain better insight into the control of melatonin physiology in man, we studied melatonin concentrations in ventricular cerebrospinal fluid (v-CSF). In four patients aged 1-4 yr with therapeutic v-CSF drainage, including one with lumbar CSF (l-CSF) drainage, CSF samples were collected sequentially over 24-hr periods. One further patient with severe sleep disturbance had one collection period under chloral hydrate and another after oral melatonin administration. Reduction of light intensity or night periods, respectively, led to increased melatonin levels. At the moment of falling asleep, additional melatonin peaks were observed in v-CSF but not in l-CSF. Oral melatonin, but not chloral hydrate, caused a rapid increase in CSF melatonin between 10 and 80 min after intake, raising levels far beyond physiological concentrations. The commencement of sleep is associated with an additional melatonin peak v-CSF which is independent of baseline secretion during the day-night cycle. The possibility is discussed that the induction of sleep might depend on a critical level or increased melatonin concentrations, which can be achieved with orally administered melatonin.

Cerebral Ventricles↗

In the rat, exogenous melatonin increases the amplitude of pineal melatonin secretion by a direct action on the circadian clock.

The effect of exogenous melatonin on pineal melatonin synthesis was studied in the rat in vivo. Daily melatonin profiles were measured by transpineal microdialysis over 4 consecutive days in rats maintained on a 12-h light : 12-h dark schedule (LD 12 : 12). Curve-fitting was used to determine the amplitude of the peak of melatonin production, and the times of its onset (IT50) and offset (DT50). A subcutaneous injection of melatonin (1 mg/kg) at the onset of darkness (ZT12) induced an advance of IT50 on the second day after the treatment, in 50% of the animals kept in LD. When the animals were switched to constant darkness, the treatment caused no detectable advance of IT50, while 70% of individuals showed a significant delay in DT50 2 days after the injection. Locally infusing the drug by reverse microdialysis into the suprachiasmatic nuclei (SCN) failed to enhance the shift in melatonin onset. Following subcutaneous melatonin injection, a significant increase ( approximately 100%) in melatonin peak amplitude was observed. This increase persisted over 2 days and occurred only when the melatonin was applied at ZT12, but not at ZT6, 17 or 22. The effect was also observed when the drug was infused directly into the SCN, but not into the pineal. Thus, the SCN are the target site for the effect of exogenous melatonin on the amplitude of the endogenous melatonin rhythm, with a similar window of sensitivity as its phase-shifting effect on the pacemaker.

Animals↗

Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats.

The effect of pineal indole hormone melatonin on colon carcinogenesis was firstly studied in rats. Two-month-old outbred female LIO rats were weekly exposed to 15 (experiment 1, groups 1 and 2) or to five (experiment 2, groups 1 and 2) s.c. injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen DMH, the rats from groups 2 (experiments 1 and 2) were given melatonin five days a week during the night-time (from 18:00 h to 8:00 h), dissolved in tap water at 20 mg/l. The experiment was finalized in 6 months after the first injection of DMH. In both experiments the majority of tumors were localized in the descending colon. Tumors of the small intestines developed only in rats from experiment 1. Total incidence of colon tumors as well as tumors in different parts of the colon and the mean number of tumors per rat were much higher in rats from both groups in experiment 1 than that in rats from experiment 2. In experiment 1 melatonin failed to influence the total incidence of colon tumors. However, incidence of carcinomas in the ascending colon was significantly reduced (P < 0.01). The multiplicity of total colon tumors per rat, as well as the mean number of tumors, ascending and descending colon per rat, was also decreased under the influence of melatonin (group 2 vs group 1, P < 0.01). In the same experiment, melatonin slightly decreased the depth of tumor invasion and increased number of highly differentiated colon carcinomas induced by DMH. The percentage of small tumours in the descending colon among rats from group 2 was higher than that of group 1. Treatment with melatonin was also followed by a decrease in the multiplicity of DMH-induced tumors of the duodenum (group 2 vs group 1, P < 0.05) and by a decrease in the incidence of jejunum and ileum tumors (group 2 vs group 1, P < 0.05). In experiment 2, the inhibitory effect of melatonin on DMH-induced colon carcinogenesis was much more expressed than that in experiment 1. Thus, in group 1 the incidence of total colon tumors, ascending and descending colon tumors, was significantly decreased in comparison with group 2; also melatonin reduced the number of tumors per rat in the ascending and descending colon. The number of colon tumors that invaded only mucosa was significantly higher in group 2 than in group 1, P < 0.05. The ratio of highly differentiated tumors was increased (P < 0.05) and the ratio of low-differentiated tumors was decreased (P < 0.05) in rats exposed to melatonin (group 4) as compared with group 3. The number of large size tumors in the ascending and descending colon was decreased whereas the number of small size tumors (<10 mm2) was increased in those parts of the colon that were under the influence of melatonin in experiment 2. Thus, our results demonstrate the inhibitory effect of melatonin on intestinal carcinogenesis induced by DMH in rats.

1,2-Dimethylhydrazine↗

Effects of different doses and durations of melatonin infusions on plasma melatonin concentrations in pinealectomized Syrian hamsters: consequences at the level of sexual activity.

The effect of different doses and durations of melatonin infusions on plasma melatonin concentrations has been studied in pinealectomized Syrian hamsters maintained under short photoperiod at either 7 degrees C or 18 degrees C. The effects of the infusions on plasma melatonin concentrations and on gonadal activity were compared. The results show that the minimal effective quantity of infused melatonin that induced gonadal atrophy was 40 ng/h at 7 degrees C and 20 ng/h at 18 degrees C. An infusion of 8 hr duration per day is necessary to inhibit sexual activity, while an infusion of 6 hr duration was ineffective. This finding suggests that the critical duration of melatonin infusion is between 6 and 8 hr. Despite the various doses of melatonin infused, plasma melatonin concentrations measured in the middle of the infusion period did not differ significantly from concentrations measured in intact animals. This finding suggests that the metabolism of infused melatonin increases as the dose of melatonin increases. Moreover, the different physiological effects observed after the various melatonin infusions cannot be explained by variations in plasma melatonin concentrations.

Animals↗

Inhibitory influence of late afternoon melatonin injections and the counter-inhibitory action of melatonin-containing pellets on thyroid growth process in male Wistar rats: comparison with effects of other indole substances.

Previous studies performed in our laboratory indicated that melatonin, when administered in late afternoon (1600-1800) as s.c. injections for 10 days, exerted an inhibitory effect on thyroid growth in mice and Sprague-Dawley rats. The goal of the present study was to examine the effects of melatonin and other indole substances (5-methoxytryptophol, N-acetylserotonin, 6-methoxytryptamine), administered for 10 days, for either 4, 8, or 10 weeks, on thyroid growth processes in adult male Wistar rats. We have also compared the action of melatonin administered in late afternoon as s.c. injections with effects of the melatonin-released chronically from s.c. implanted beeswax pellets containing 1 mg of the hormone. Additionally, the effects of melatonin injections in animals with the pineal gland removed and in thyroid stimulating hormone (TSH)-injected rats have been studied. We examined the mean mitotic activity rates (MMARs) of thyroid follicular cells (TFC) and the wet thyroid weights. We concluded that melatonin, of the examined substances, is the most potent inhibitor of thyroid growth; the hormone reduced the MMAR of TFC and the thyroid weight at all time-points. 5-Methoxytryptophol, like melatonin, exerted the inhibitory influence on the mitotic activity; however, it did not affect thyroid weight. The influence of other indole substances was much less pronounced. It was shown that melatonin-pellets prevented the inhibitory effect of late afternoon melatonin injections on thyroid growth processes. This observation is consistent with results of other authors concerning the counter-antithyroid effect of melatonin on thyroid hormone secretion. Pinealectomy revealed the stimulatory effect on thyroid growth processes, while melatonin treatment reversed the effect of the surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of serotonin and melatonin in gastrointestinal physiology: ontogeny, regulation of food intake, and mutual serotonin-melatonin feedback.

Average levels of melatonin in the brain and the gastrointestinal (GIT) tissues of newborn mice declined dramatically during the first week postnatally. Food consumption increased considerably in mice bearing subcutaneous serotonin (5-HT) implants (2 mg). Melatonin implants (2 mg) also increased overall consumption but to a lesser degree. Both 5-HT and melatonin implants (2 mg) increased water content of mice fecal pellets, albeit the melatonin effect was less pronounced. Serotonin implants (2,4,6 mg/mouse) increased melatonin levels in brain, jejunum, ileum, and colon, but the effect was not dose-dependent. Intraperitoneally administered melatonin (5, 20 and 200 ug/mouse) elevated melatonin levels in brain and GIT tissues more than 100 times that of the controls, but the effect was not dose-dependent. In contrast, intraperitoneal administration of melatonin (5, 50, and 200 ug) in mice bearing a 5-HT implant (2 mg) resulted in only 3-7 times higher melatonin levels in the GIT as compared to controls, and the brain levels of melatonin were actually lower. A feedback system between 5-HT and melatonin is proposed that regulates appetite and digestive processes by endocrine as well as paracrine effects in both the brain and the GIT.

Animals↗

Diurnal changes in plasma melatonin and the timing of reproductive onset in anestrous sheep fed melatonin.

Seasonally anestrous Suffolk ewes (n = 28) were randomly divided into 5 groups and treated with varying doses of melatonin as follows; Groups C (n = 4), M1 (n = 6), M2 (n = 6), M3 (n = 6), M4 (n = 6) of ewes were fed pellets containing 0, 1, 2, 3 and 4 mg melatonin, respectively, daily for 60 days from May 17 (Day 0). Following feeding of the pellets at 13.00 hr plasma levels of melatonin rapidly increased reaching the peak values within 30 min, which ranged from 92.0 to 292.7 pg/ml and were highly correlated with the dose of melatonin administered (r = 0.986, P less than 0.01). Maximum dose of melatonin (4 mg) produced an increase of plasma melatonin similar in magnitude to nocturnal peaks of endogenous secretion. The onset of ovulatory cyclicity, assessed from plasma progesterone profiles, was advanced by melatonin administration. The mean +/- SEM intervals from the commencement of melatonin treatment until the onset of ovulatory cyclicity were 53.0 +/- 5.8, 53.6 +/- 2.5, 42.0 +/- 5.6 and 44.3 +/- 4.3 days for the Groups M1, M2, M3 and M4, respectively, which were shorter (M1, P less than 0.05; M2, M3 & M4, P less than 0.01) than that for the Group C (72.5 +/- 1.4 days). The melatonin treatment also suppressed, in a dose related manner, the rise in plasma prolactin under the lengthening photoperiod. We conclude that the dose-related efficacy of melatonin could be ascribed to the difference in the diurnal profiles of circulating melatonin.

Administration, Oral↗

The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement.

The present investigation used a placebo-controlled, double-blind, crossover design to assess the sleep-promoting effect of three melatonin replacement delivery strategies in a group of patients with age-related sleep-maintenance insomnia. Subjects alternated between treatment and "washout" conditions in 2-week trials. The specific treatment strategies for a high physiological dose (0.5 mg) of melatonin were: (1) EARLY: An immediate-release dose taken 30 minutes before bedtime; (2) CONTINUOUS: A controlled-release dose taken 30 minutes before bedtime; (3) LATE: An immediate-release dose taken 4 hours after bedtime. The EARLY and LATE treatments yielded significant and unambiguous reductions in core body temperature. All three melatonin treatments shortened latencies to persistent sleep, demonstrating that high physiological doses of melatonin can promote sleep in this population. Despite this effect on sleep latency, however, melatonin was not effective in sustaining sleep. No treatment improved total sleep time, sleep efficiency, or wake after sleep onset. Likewise, melatonin did not improve subjective self-reports of nighttime sleep and daytime alertness. Correlational analyses comparing sleep in the placebo condition with melatonin production revealed that melatonin levels were not correlated with sleep. Furthermore, low melatonin producers were not preferentially responsive to melatonin replacement. Total sleep time and sleep efficiency were correlated with the timing of the endogenous melatonin rhythm, and particularly with the phase-relationship between habitual bedtime and the phase of the circadian timing system.

Age Factors↗

Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists.

Circadian rhythm sleep disorders (CRSDs), whether chronic or transient, affect a broad range of individuals, including many elderly, those with severe visual impairments, shift workers, and jet travelers moving rapidly across many time zones. In addition, various forms of insomnia affect another large sector of the population. A feature common among CRSDs and some forms of insomnia is sensitivity to the hormone melatonin, which is secreted by the pineal gland. Accumulating evidence suggests that melatonin may regulate the circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the light-dark cycle is the primary signal that entrains the circadian clock to environmental cycles, exogenous melatonin has been shown to entrain the clock in individuals with no light perception and free-running circadian rhythms. Furthermore, studies have reported beneficial effects of melatonin for treatment of certain insomnias. Together, these studies suggest that melatonin may be useful for treating some insomnias and CRSDs. In these contexts, use of melatonin as a supplement has been popular in the United States. Unfortunately, the therapeutic potential of melatonin has been difficult to realize in clinical trials, possibly owing to non-specific actions of the agent and its unfavorable pharmacokinetic properties when administered orally. In an attempt to take advantage of the therapeutic opportunities available through the brain's melatonin system, researchers have developed several melatonin agonists with improved properties in comparison to melatonin. Some of these agents are now in clinical trials for treatment of insomnia or CRSDs.

Acetamides↗

Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude.

In this study we have examined the ability of melatonin and four synthetic melatonin receptor agonists to entrain endogenous melatonin secretion in rats, free running in constant darkness. The circadian melatonin profile was measured by trans-pineal microdialysis, which not only reveals the time of onset and end of production (phase), but also the amplitude of the rhythm. Exogenous melatonin given at the onset of subjective darkness (clock time 12 h) was effective to entrain endogenous melatonin production. Only one agonist, 2-chloroacetamido-8-methoxytetralin (AH-017), mimicked this action. Two other agonists, 4-methoxy-2-(methylene propylamide)indan (GG-012) and N-[2-[2,3,7,8-tetrahydro-1H-furo(2, 3-g)indol-1-yl]ethyl]acetamide (GR196429), induced a phase-delay under free running conditions, possibly by increasing tau (tau) period. One agonist, 2-acetamido-8-methoxytetralin (AH-001) did not show any phase effect on the free running rhythm. Unexpectedly, all melatonin receptor agonists increased the amplitude of melatonin secretion. The amount of the increase varied from just below the level of significance (AH-001) to an approximately 2-fold increase (GG-012 and GR196429). This is in clear contrast to entrainment with melatonin, which significantly decreased the amplitude. It is hypothesized that entrainment and effects on amplitude of melatonin secretion are mediated by different mechanisms which can be differentially modulated using specific ligands.

Animals↗

Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor.

A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel1a melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel1b melatonin receptor. The Mel1b receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel1a receptor. Transient expression of the Mel1b receptor in COS-1 cells results in high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel1a melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel1b melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel1b melatonin receptor is expressed in retina and, to a lesser extent, brain. PCR analysis of human-rodent somatic cell hybrids maps the Mel1b receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel1b melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals.

Amino Acid Sequence↗

MT-1 melatonin receptor expression increases the antiproliferative effect of melatonin on S-91 murine melanoma cells.

Melatonin, a derivative of tryptophan that is present in all vertebrates, was first described in bovine pineal gland. It is known that melatonin is a highly conserved molecule, present also in unicellular organisms and plants. Several effects of melatonin have been described, including receptor- and non-receptor-mediated actions. Herein, we studied the effects of melatonin on in vitro and in vivo cell proliferation of Cloudman S-91 murine melanoma cells. We demonstrated that melatonin treatment significantly inhibits S-91 melanoma cell proliferation in vitro (EC50 = 10-7 m) as well as reduces tumor growth in vivo. We also demonstrated that melatonin directly increases the activity of the antioxidant enzymes catalase and glutathione peroxidase. These effects are most likely triggered through the direct intracellular action of melatonin, since the presence of receptors could not be demonstrated in this cell line. Expression of MT-1 melatonin receptor by stable transfection, mediated a dramatic antiproliferative melatonin effect (EC50 = 10-10 m) in S-91 cells. The expressed receptor is negatively coupled to the adenylyl cyclase/cyclic AMP signaling pathway via Gi protein. These results suggest that expression of the MT-1 melatonin receptor in melanoma cells is a potential alternative approach to specifically target cells in cancer therapeutic treatment.

Animals↗

Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status.

There are functional inter-relationships between the beta cells of the endocrine pancreas and the pineal gland, where the synchronizing circadian molecule melatonin originates. The aim of this study was to elucidate a putative interaction between insulin and melatonin in diabetic patients and a diabetic rat model. We analyzed glucose, insulin, and melatonin levels of type 2 patients, as well as type 2 diabetic Goto Kakizaki (GK) rats by radioimmunoassay. Expression of pancreatic melatonin and pineal insulin receptors, as well as arylalkylamine-N-acetyltransferase (AANAT), was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The AANAT enzyme activity was measured in pineal homogenates. Diabetic patients showed a decrease in melatonin levels, while in the pancreas of GK rats an upregulation of the melatonin-receptor mRNA was determined. The pancreatic islets of GK rats showed expression of the mRNA for the pancreatic melatonin (MT1) receptor, which had previously been identified in rats and insulinoma (INS1) cells. Besides their presence in animal cells, the MT1-receptor transcript was also detected in human pancreas by RT-PCR. Whereas the rat pancreatic mRNA expression of the MT1-receptor was significantly increased, the activity of the pineal AANAT enzyme was reduced. The latter observation was in accordance with plasma melatonin levels. The insulin-receptor mRNA of the pineal gland was found to be reduced in GK rats. Our observations suggest a functional inter-relationship between melatonin and insulin, and may indicate a reduction of melatonin in the genesis of diabetes.

Animals↗

The circadian clock, light/dark cycle and melatonin are differentially involved in the expression of daily and photoperiodic variations in mt(1) melatonin receptors in the Siberian and Syrian hamsters.

Mechanisms underlying the daily and photoperiodic variations in mt(1) melatonin receptors were investigated in the pars tuberalis (PT) and suprachiasmatic nuclei (SCN) of Siberian and Syrian hamsters. Whatever its daily profile, melatonin receptor density was strongly increased in both structures and species after constant light exposure or pinealectomy, and decreased after a single melatonin injection, indicating melatonin involvement in the daily regulation of the receptor protein. This was confirmed by a strong inverse correlation between melatonin binding capacity and plasma melatonin concentration. In contrast, regulation of mt(1) mRNA appeared more complex. The circadian clock, the light/dark cycle and melatonin are all implicated in mt(1) gene daily fluctuations, but the extent of their involvement depends upon the structure and the species studied. The photoperiodic decrease in melatonin receptor density observed in short photoperiod (PT of the two hamster species and Syrian hamster SCN) seems to be the consequence of a long-term mt(1) gene repression induced by the lengthening of the melatonin peak. Altogether, these results show that during daily variations, mt(1) melatonin receptor mRNA and protein are differentially regulated, while at the photoperiodic level, the mt(1) protein status depends on mRNA transcription.

Animals↗

Exogenous melatonin fails to counteract the light-induced phase delay of human melatonin rhythm.

Salivary melatonin levels were measured in 6 healthy volunteers in order to determine whether the phase shift caused by a single 60-min light pulse of 2000 lux might be inhibited by maintaining high melatonin concentration. In the control sessions, the samples were collected at 60-min intervals under lighting of < 10 lux from 18.00 to 11.00 h. In the light-exposure sessions, placebo or 0.5 mg melatonin was administered orally 60 min prior to the light pulse, timed at the rising phase of the melatonin synthesis. The after-light sessions, one day after the light exposure, were like the control sessions. The average delays of the melatonin half-rise and half-decline times were equal (about 0.7 h) in the placebo and melatonin replacement experiments. The maintenance of high melatonin levels during the light exposure did not counteract the influence of bright light on the melatonin rhythm. Thus, in the adjustment of the melatonin rhythm, light is a stronger regulator than melatonin itself.

Adult↗

Effect of melatonin replacement on serum hormone rhythms in a patient lacking endogenous melatonin.

A potentially confounding variable inherent in studies designed to examine the effect of melatonin administration in humans is the presence of an endogenous melatonin rhythm in the experimental subjects. The effects of exogenous melatonin administration on serum hormone rhythms was recently examined in a male patient who lacked detectable circulating levels of endogenous melatonin. The patient's pineal gland had been destroyed five years previously in the course of treatment for a pineal astrocytoma. On three separate occasions, over approximately a one-year period, the patient was given daily oral melatonin replacement (2 mg/day, 1 mg/day and 0.5 mg/day). These experiments were designed to assess the effects of exogenous melatonin on serum growth hormone, prolactin, cortisol and testosterone rhythms. Analysis of blood samples collected every 2-4 hours periods both before and during melatonin replacement revealed that the exogenous melatonin rhythm was associated with improvements in self-reported sleep and mood ratings. Melatonin administration produced robust nocturnal peaks in serum growth hormone and prolactin levels immediately following ingestion of the hormone, while serum cortisol and testosterone rhythms were not influenced. These results suggest that melatonin may modulate the coordination and enhancement of selected biological rhythms in man.

Adult↗

Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood.

OBJECTIVE: We investigated whether melatonin is present in walnuts (Juglans regia L.) and, if so, tested whether eating walnuts influences melatonin levels and the total antioxidant status of the blood. METHODS: Melatonin was extracted from walnuts and quantified by high-performance liquid chromatography. After feeding walnuts to rats, serum melatonin concentrations were measured using a radioimmunoassay and the "total antioxidant power" of the serum was estimated by using the trolox equivalent antioxidant capacity and ferric-reducing ability of serum methods. RESULTS: Mean +/- standard error melatonin concentrations were 3.5 +/- 1.0 ng/g of walnut. After food restriction of rats and then feeding them regular chow or walnuts, blood melatonin concentrations in the animals that ate walnuts were increased over those in the rats fed the control diet. Increases in blood melatonin were also accompanied by increases in trolox equivalent antioxidant capacity and ferric-reducing ability of serum values. CONCLUSIONS: Melatonin is present in walnuts and, when eaten, increase blood melatonin concentrations. The increase in blood melatonin levels correlates with an increased antioxidative capacity of this fluid as reflected by augmentation of trolox equivalent antioxidant capacity and ferric-reducing ability of serum values.

Animals↗

Influence of light environment and photoperiod on plasma melatonin and cortisol profiles in young domestic boars, comparing two commercial melatonin assays.

Eighteen crossbred boars, three siblings from each of six litters, were distributed randomly among three groups after weaning. The 'Natural long-day' group was housed in a standard room with windows, whereas the 'Artificial long-day' and 'Artificial short-day' groups were housed in light-sealed rooms and under an artificial light regimen (1400 lx). In spring (16-17 hr of light) plasma levels of melatonin and cortisol were measured in samples collected hourly for 24 hr. Two commercial melatonin radioimmunoassays with preassay diethyl ether extraction were compared. Only the assay from Bühlmann Laboratories AG showed low to undetectable melatonin levels during the light-phase and was used for further analysis. Dark-phase melatonin concentrations were higher than light-phase melatonin concentrations (P < 0.001). Dark-phase melatonin concentrations were higher in the 'Natural long-day' group than in the 'Artificial long-day' and the 'Artificial short-day' groups (P < 0.001). Sire had a significant effect on dark-phase melatonin concentrations (P < 0.01), but not on light-phase levels. Cortisol concentrations were higher during the light-phase than during the dark phase, and light-phase cortisol concentrations were higher in the 'Natural long-day' group than in the 'Artificial long-day' and the 'Artificial short-day' groups (P < 0.01). This study showed that peripubertal boars express a typical circadian melatonin rhythm under both artificial light regimens and in standard pig stable environment. Natural photoperiod and indoor lighting seem to interact in shaping the melatonin profile in standard stable environment. The great individual variation in the amplitude of the dark-phase melatonin levels could in this study be explained by the different sires.

Animals↗