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At least 19 recordsLinked to original sources

PubMed1990

Melatonin receptors and signal transduction in melatonin-sensitive and melatonin-insensitive populations of white-footed mice (Peromyscus leucopus).

The pineal hormone melatonin times seasonal alterations in reproductive function in photoperiodic mammals. In white-footed mice, there is variation in responsiveness to the reproductive effects of melatonin between populations originating in different locations; mice from Connecticut (CT) respond normally to melatonin, while mice from Georgia (GA) appear insensitive to melatonin. In the present paper, we compare melatonin receptor distribution and a second messenger response to melatonin in white-footed mice from CT and GA. Specific binding of 125I-labeled melatonin (I-MEL) was observed in a variety of brain regions in each population, but there were no consistent differences in the distribution or intensity of I-MEL binding between the populations. Furthermore, melatonin inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis explants from both populations. These results suggest that insensitivity to melatonin in GA mice is not due to a gross defect in melatonin receptors or receptor-effector coupling.

Animals↗

PubMed1990

Fluctuation of blood melatonin concentrations with age: result of changes in pineal melatonin secretion, body growth, and aging.

Melatonin in the systemic circulation of rats fluctuates with age, and the causes for such changes were investigated. Male rats (aged 7 days, 16 days, 18 days, 20 days, 30 days, 48 days, 60 days, and greater than 17 months) were adapted under a lighting regime of 12L:12D for at least 7 days. Pineals and blood samples from the trunk or confluens sinuum were collected in the dark period. Melatonin in tissues was extracted, identified, and determined by gas chromatography-mass spectrometry (GC-MS) and/or radioimmunoassay. Tissue melatonin levels obtained by radioimmunoassay correlated closely with those quantified by GC-MS. Thus, the melatonin radioimmunoassay used is a reliable assay method for melatonin in the plasma and pineal of the rat. Plasma melatonin in the confluens sinuum of rats exhibited episodic release superimposed on a basal release pattern. It was suggested that there are two pools of melatonin in the pineal gland, a readily releasable pool and a bound pool. The mean plasma levels of melatonin in the confluens sinuum of rats increased with age with the highest level recorded at 60 days old and declined to a lower level at greater than 17 months old. The above age-related changes, being similar to the alterations in pineal melatonin levels with growth and aging, suggest that, under our experimental conditions, levels of pineal melatonin increase or decrease with its secretory rate. In developing rats, the age-related increase in the rate of secretion of pineal melatonin as reflected by increases in melatonin levels in the confluens sinuum or pineal melatonin content before adulthood is different from the changes in melatonin levels in the systemic circulation which showed an early developmental rise, followed by an active period and then a prepubertal decline. However, when the body weight was taken into consideration, changes in the levels of pineal melatonin content per 100 gm body weight or the calculated blood melatonin levels (plasma melatonin in the confluens sinuum/body:head ratio) correlated well with the fluctuation of serum melatonin in the systemic circulation. Thus, the developmental changes in the concentrations of melatonin in the general circulation are the result of 1) changes in the rate of pineal melatonin secretion and 2) increase in the dilution factor because of increase in body size. In old rats, levels of plasma melatonin in the confluens sinuum and pineal melatonin content decreased indicating a decline in the rate of pineal melatonin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1991

Human plasma melatonin and urinary 6-sulphatoxy melatonin: studies in natural annual photoperiod and in extended darkness.

OBJECTIVES: The aims of the study were (1) to examine the human plasma melatonin rhythm at the equinoxes and the solstices in the natural photoperiod (at 35 degrees S); (2) to examine melatonin rhythms in the same subjects under extended darkness conditions to expose any suppressive (gating) effects of light at any time of the year; (3) to undertake a rigorous examination of the relationship between plasma melatonin and the urinary metabolite 6-sulphatoxy melatonin at varying times of the year. DESIGN: At the equinoxes and solstices, unrestricted subjects had hourly urine collections followed by venous blood sampling taken under natural light conditions for 24 hours. Following a 24 hour interval, a similar collection regime was performed with subjects held under conditions of extended darkness (5 hours darkness prior to natural sunset and following natural sunrise) for a further 24 hours. SUBJECTS: Groups of four (minimum) to six female volunteers (age range 18-35 years) were studied, who had a normal lifestyle, no history of depression, and were not taking any medication or recently engaged in shiftwork. MEASUREMENTS: The plasma was assayed for melatonin and the urine samples for 6-sulphatoxy melatonin by radioimmunoassay. RESULTS: The onset of natural melatonin secretion was delayed until after sunset at all seasons but was earlier in summer, and not different from the time of sunset in extended darkness. The offset of melatonin secretion under natural conditions occurred at sunrise in autumn and winter but was delayed until after sunrise during spring and summer, particularly in extended darkness. No significant changes in the duration of melatonin secretion were observed between seasons nor between the duration of melatonin secretion under natural photoperiod or extended darkness. The measurement of 6-sulphatoxy melatonin proved to be a close indicator of the phase and amplitude of secretion of plasma melatonin. Both onset and offset times of 6-sulphatoxy melatonin were delayed compared to the times when plasma melatonin was detectable/undetectable. A good correlation exists between the total plasma melatonin secretion and that of 6-sulphatoxy melatonin. CONCLUSIONS: The results suggest evidence for a suppressive (gating) effect of light at dawn only during summer which was associated with a phase advance of the onset of melatonin secretion at this time of year. The lack of a major gating effect of environment light on melatonin secretion, and the unchanging duration of secretion through the year in the normally entrained human, highlight differences between the human and those photoperiodic animal species which breed seasonally. Urinary 6-sulphatoxy melatonin proved to be a good indicator of plasma melatonin levels under rigorous examination and is confirmed as a useful clinical measure.

Adolescent↗

PubMed1990

Effects of short-day photoperiods and of N-(2,4-dinitrophenyl)-5-methoxytryptamine, a putative melatonin antagonist, on melatonin synthesis in the Harderian gland of the Syrian hamster, Mesocricetus auratus.

The Harderian glands of Syrian hamsters contain melatonin and the enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) which synthesize melatonin from serotonin. Because the Harderian glands share this metabolic pathway with the pineal gland, we examined the effects of short-day photoperiods, which stimulate pineal-mediated gonadal regression, and N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23), which has been described as a melatonin antagonist, on melatonin synthesis in the Harderian glands of the hamster. Harderian glands of male hamsters kept in short days had reduced NAT activity and melatonin concentration, but HIOMT activity was unchanged from that of long-day controls. In males kept in short days, ML-23 restored melatonin concentrations to levels seen in long days but did not affect the short-day induced reduction in NAT activity. ML-23 had no effect upon NAT or HIOMT activity or melatonin concentration in male hamsters kept on long days. Harderian glands of female hamsters kept on short days had reduced melatonin concentrations, but NAT and HIOMT activities similar to those of long-day controls. ML-23 had no effect on Harderian NAT or HIOMT activities or melatonin concentration in females kept in short days. However, in females kept in long days, ML-23 treatment led to increased NAT activity and decreased melatonin concentrations. We conclude from these results that short-day photoperiods alter some aspects of melatonin synthesis in hamster Harderian glands and that these effects differ in males and females. ML-23 does not usually prevent the effects of short days on Harderian melatonin synthesis, suggesting that it is not a melatonin antagonist in the Syrian hamster.

5-Methoxytryptamine↗

PubMed1990

Correlation between salivary and serum melatonin: dependence on serum melatonin levels.

Saliva and serum samples were collected from eight healthy volunteers every two hours during a 26-hour period. Melatonin concentrations were measured by radioimmunoassay after chloroform extraction using radioiodinated melatonin as a tracer. Five of the subjects had high serum melatonin levels at night (peak levels higher than 75 pg/ml); in three subjects the highest serum melatonin concentration was 20-40 pg/ml. All subjects had low levels (less than 10 pg/ml) during the day. The correlations between salivary and serum levels were calculated. The regression line y = 0.33x + 3.7 pg/ml, r = 0.95, P less than 0.001, was obtained for all detectable value pairs (n = 73). The regression and correlation coefficients were almost equal for the peak values of melatonin and during the rising and descending phases of the secretion patterns. However, no significant correlation was found between low daytime salivary and serum concentrations when calculated separately. In the five high-secretors the melatonin levels in saliva reflected reliably the changes in serum, but in the three low-secretors the correlation between salivary and serum melatonin was not significant. The proportion of melatonin found in saliva decreased with increasing serum melatonin levels. Circadian rhythm parameters were estimated by single cosinor analysis. The acrophases did not differ significantly within a subject in the concomitant measurements of serum and salivary melatonin. The measurements of salivary melatonin levels seem valid for studies on melatonin rhythms, but the melatonin concentrations measured in saliva do not always consistently reflect the absolute concentrations in blood.

Adult↗

PubMedDate not supplied

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

Diurnal changes in serum melatonin concentrations under indoor and outdoor environments and light suppression of nighttime melatonin secretion in the female Japanese monkey.

To examine whether artificial light with the intensity commonly used for animal experimentation can mimic natural sunlight with respect to diurnal changes in serum melatonin, and to determine the minimum light intensity required to suppress nocturnal melatonin, serum melatonin profiles were examined in groups of female Japanese monkeys (Macaca fuscata fuscata). Under outdoor environment, light intensities at the level of the monkey's eyes varied during daytime (0900-1500 h) depending on weather conditions (minimum and maximum on particular experimental days: 170 lux at 0900 h on a rainy day and 9500 lux at 0900 h on a slightly cloudy day); under indoor environment, light was provided by ordinary fluorescent bulbs that resulted in intensities of 400-500 lux at the level of monkey's eyes. No difference was found in diurnal changes in serum melatonin concentrations regardless of weather or housing conditions: Serum melatonin remained low during daytime and increased during nighttime. Following exposure to light, irradiances of 10,000, 400-500, 100-140, 50-100, and 10-30 lux at midnight resulted in a rapid decrease in serum melatonin to daytime levels within 1 to 2 h. After the onset of dark, serum melatonin reverted to previous nighttime levels within 2 h. Exposure to a light irradiance of 2-5 lux, however, did not suppress nocturnal melatonin secretion. It is concluded that artificial light can mimic natural sunlight with respect to melatonin secretion in the female Japanese monkey, and that light of 10-30 lux irradiance was sufficient to suppress serum melatonin to near daytime levels.

Animals↗

PubMedDate not supplied

Inhibition of human platelet aggregation and thromboxane B2 production by melatonin. Correlation with plasma melatonin levels.

Plasma melatonin concentrations and the effect of melatonin on arachidonic acid (AA)-induced aggregation and thromboxane B2 (TxB2) production by platelet-rich plasma (PRP) were examined in five normal male volunteers, sampled at 2 hr intervals from 21:30 to 09:30 hr. Peak plasma melatonin concentration was found at 03:30 hr. Inhibition by 10(-6) M melatonin of AA-induced PRP aggregation was observed only in samples taken at 01:30 hr. Assessment of the inhibitory effect of 10(-9)-10(-6) M melatonin on AA-induced TxB2 production indicated that melatonin activity was greater at 01:30 h as compared to late night. Assessed as a global effect, the inhibitory activity of melatonin on PRP TxB2 showed a maximum at 01:30 hr and minimal effects at 03:30 hr, at the time when plasma concentrations of melatonin were highest. These results indicate the existence of a nocturnal variation in sensitivity of human platelets to melatonin, with a peak that precedes the maximum in circulating melatonin levels.

Adult↗

PubMed1978

Transport of maternal[3H]melatonin to suckling rats and the fate of [3H]melatonin in the neonatal rat.

The question of whether maternal melatonin could be transported in milk to suckling rats was investigated because melatonin is probably not produced in these animals during the first 10 days of life. [3H]Melatonin was found to be rapidly transferred from the maternal circulation into lactating mammary tissue, and the stomach of each suckling rat was found to contain [3H]melatonin. To study the fate and tissue distribution of [3H]melatonin originating in the neonatal stomach, suckling rats were given [3H]melatonin by stomach tube; [3H]melatonin was recovered from plasma and seven tissues, including brain, 15 and 60 min later. The general tissue distribution of [3H]melatonin was similar to that found in adult rats. The major [3H]melatonin metabolites in the urine of suckling rats, as the adult rats, were the conjugates of 6-hydroxy-melatonin.

Animal Population Groups↗

PubMed1978

Physiological control of melatonin synthesis and secretion: mechanisms, generating rhythms in melatonin, methoxytryptophol, and arginine vasotocin levels and effects on the pineal of endogenous catecholamines, the estrous cycle, and environmental lighting.

Daily rhythms in pineal methoxyindole metabolism have been described in rodents and humans: serotonin levels in rat pineals are highest during the daylight hours and fall markedly soon after the onset of darkness, coincident with increases in the levels of pineal melatonin and 5-methoxy-tryptophol and the activities of pineal serotonin-N--acetyltransferase (SNAT) and hydroxyindole-O-methyltransferase (HIOMT). The fact that the levels of melatonin and 5-methoxytryptophol vary in parallel suggests that the major factor generating the methoxyindole rhythms is not SNAT activity, as has been suggested, but a proximal step, perhaps a change in the availability (for metabolism) of "stored" serotonin. Melatonin levels in human serum and urine exhibit rhythms similar to those observed in rats, i.e., they rise sharply during the daily dark period. When the onset of darkness is delayed by 12 hours, human melatonin rhythms usually require 3 or 4 days to adjust to the new lighting regimen. Environmental factors, other than light, that activate the sympathetic nervous system or cause epinephrine to be secreted from the adrenal medulla (e.g., the stress of immobilization; insulin-induced hypoglycemia) can override the inhibitory effects of light and accelerate melatonin synthesis. Melatonin levels in rat blood and urine are lowest during the proestrous and estrous phases of the estrous cycle. Although this effect of the ovarian steroid hormones is accompanied by a reduction in urinary norepinephrine levels, it is not caused simply by a decrease in the quantity of norepinephrine acting on the pineal but also involves a direct action of the hormones. Ovariectomy increases serum melatonin levels, whereas the administration of estradiol plus progesterone (to ovariectomized animals) lowers melatonin levels. The spectral and intensity-response characteristics of the photic inhibition of melatonin synthesis have been established for the rat. Rhythms in melatonin synthesis apparently persist among animals placed in environments of continuous darkness; the source of the cyclic signal (mediated by the pineal sympathetic nerves) has not yet been identified. Preliminary evidence suggests that levels of a peptide hormone, arginine vasotocin, in rat pineals and sera also exhibit daily rhythms and are increased by norepinephrine.

Animals↗

PubMed1992

Melatonin increases serotonin N-acetyltransferase activity and decreases dopamine synthesis in light-exposed chick retina: in vivo evidence supporting melatonin-dopamine interaction in retina.

The administration of melatonin, either peripherally (0.01-10 mg/kg) or intraocularly (0.001-10 mumol/eye), to light-exposed chicks dose-dependently increased serotonin N-acetyltransferase (NAT) activity in retina but not in pineal gland. The effect of melatonin was slightly but significantly reduced by luzindole (2-benzyl-N-acetyltryptamine), and not affected by two other purported melatonin antagonists, N-acetyltryptamine and N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23). The elevation of the enzyme activity induced by melatonin was substantially stronger than that evoked by 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, or 5-methoxytryptamine. The melatonin-evoked rise in the retinal NAT activity was counteracted by two dopamine D2 receptor agonists, quinpirole and apomorphine, and prevented by the dopamine D2 receptor blocker spiroperidol, and by an inhibitor of dopamine synthesis, alpha-methyl-p-tyrosine. Melatonin (0.1-10 mg/kg i.p.) dose-dependently decreased the levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), as well as the DOPAC/dopamine ratio, in chick retina but not in forebrain. The results obtained (1) indicate that melatonin in vivo potently inhibits dopamine synthesis selectively in retina, and (2) suggest that the increase in retinal NAT activity evoked by melatonin in light-exposed chicks is an indirect action of the compound, and results from the disinhibition of the NAT induction process from the dopaminergic (inhibitory) signal. The results provide in vivo evidence supporting the idea (derived on the basis of in vitro findings) that a mutually antagonistic interaction between melatonin and dopamine operates in retinas of living animals.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Identification of a seasonal elevation in daytime melatonin levels associated with the rut in fallow bucks (Dama dama): the effect of day length and exogenous melatonin.

The timing of the seasonal reduction in voluntary food intake and hormonal changes associated with the rut were investigated in mature fallow bucks subjected to artificial long-day exposure with and without superimposed melatonin-releasing implants. Circulating testosterone profiles and the period of inappetence, signalling the onset of the period of reproductive activity in untreated bucks under natural photoperiod, were phase-advanced in both treatment groups. In the long-day treated group, these profiles were phase-advanced by 1 week, while in the long-day + melatonin group, the phase advance was 6 weeks compared to the controls. Circulating daytime melatonin, elevated in all three groups, corresponds with seasonal changes in circulating testosterone levels associated with the rut. Prolactin profiles followed ambient photoperiod, being high during natural or artificial long days and low during natural short days. Exogenous melatonin administered during long-day exposure initiated a rapid and reversible decrease in circulating prolactin levels. The elevation in plasma melatonin could not be separated temporally from the seasonal testosterone peak by exposure to long days or to exogenous melatonin. However, this daytime melatonin profile was abolished by the ablation of circulating testosterone following immunization against luteinizing hormone releasing hormone (LHRH). The presence of this endogenous melatonin during daylight was observed only during the rut, as measured in two radioimmunoassays and confirmed by mass spectrometry. It is likely that both testosterone and melatonin influence the onset of the seasonal rut in fallow bucks.

Animals↗

PubMed1986

Characterization of central melatonin receptors using 125I-melatonin.

The binding of 125I-melatonin, a potent analog of melatonin, to rat brain synaptosomal preparations was investigated. 125I-melatonin bound with high affinity (Kd = 38 nM) to a single class of sites (Bmax = 81 fmol/mg protein). Kinetic studies indicated that binding was time-dependent and reversible. Specific 125I-melatonin binding was inhibited by melatonin, and was unaffected by other structurally related compounds including serotonin. Binding of 125I-melatonin was greatly reduced if the synaptosomal preparations were pretreated by heat or trypsin but was unaffected by freeze-thawing. These results suggest that 125I-melatonin may serve as a valuable probe for studying melatonin receptors.

Animals↗

PubMed1992

Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract.

The administration of L-tryptophan (Trp, 150-300 mg/kg) to rats and chicks causes a rapid and dose-dependent elevation of circulating melatonin. The elevation of serum melatonin was greater after oral compared to the intraperitoneal route of administration of the same dose of Trp (150 mg/kg). The Trp-induced increase of circulating melatonin was unaffected by prior pinealectomy but was almost abolished by a partial ligature of the portal vein. The Trp-induced increase of melatonin in the portal blood preceded that in the systemic circulation. The gut contains considerable amounts of melatonin and the Trp-induced elevation of melatonin was greater in the duodenum compared to the pineal or the blood. The enterochromaffin cells of the gastrointestinal tract appear to be the major source of the Trp-induced increment of circulating melatonin. The possibility is discussed that the sedating, sleep inducing effects of Trp are mediated by the Trp-induced elevation of circulating melatonin.

Administration, Oral↗

PubMed1976

Effect of melatonin on the reproductive systems of male and female Syrian hamsters: a diurnal rhythm in sensitivity to melatonin.

Hamsters were maintained on a long photoperiod (14L:10D) and were injected once daily with melatonin (10-25 mug) or sesame oil. Males which received melatonin during the afternoon (e.g., 6.5-13.75 h after lights-on) showed regressed testes and decreased levels of serum LH and FSH after several weeks of treatment. Injections of the oil vehicle or injections of melatonin given in the morning (3 h after lights-on) had no detectable effect on testicular size or on serum gonadotropins. Females which received melatonin during the afternoon became acyclic after several weeks of treatment and showed a diurnal pattern of LH secretion. The acyclic females required 4-6 weeks to resume estrous cyclicity following termination of the melatonin injections. The effects of melatonin on gonadal function and on serum gonadotropin concentrations in both sexes were similar to the previously observed effects of prolonged exposure to short photoperiods. These results indicate that chronic daily injections of melatonin can depress reproductive function in hamsters and that the effectiveness of the injections is dependent upon the time of day at which they are administered.

Animals↗