Variations In Melatonin Levels Research Articles

Salivary Melatonin Rhythm and Prostate Cancer: CAPLIFE Study.

We analyzed the association between salivary melatonin rhythm and prostate cancer (PCa). A total of 40 PCa cases and 41 controls from the CAPLIFE study were analyzed to determine the salivary melatonin rhythm through 6 saliva samples. Amplitude (maximum melatonin peak) was categorized as low or high using the cutoff point median of the controls. Acrophase (time of maximum melatonin peak) was classified as early or late using the same criteria. In addition, the following data were collected: characteristics related to sleep habits, and clinical and sociodemographic information. Melatonin rhythms were represented for cases and controls and analyzed according to urinary symptoms, tumor aggressiveness and tumor extension. Variations in melatonin levels were estimated using generalized estimating equations on the ln-transformed values. To estimate the association between amplitude, acrophase and PCa, adjusted odds ratio (aOR) and 95% CI were calculated using logistic regression models. The mean age was 67.0 years (SD 7.3) for cases and 67.5 (SD 5.5) for controls. Melatonin levels were always lower in PCa cases than in controls. On average, melatonin levels in cases were -64.0% (95% CI -73.4, -51.4) than controls. PCa cases had lower amplitude, 26.0 pg/ml (SD 27.8) vs 46.3 pg/ml (SD 28.2; p <0.001). A high amplitude was associated with a decreased risk of PCa, aOR=0.31 (95% CI 0.11, 0.86), while a late acrophase could be increased risk of PCa, aOR=2.36 (95% CI 0.88, 6.27). Patients with PCa always had lower melatonin levels than men without PCa, independent of urinary symptomatology or extension and aggressiveness of the tumor.

Variations in melatonin levels in preterm and term human breast milk during the first month after delivery

The objectives of the present study were to examine the dynamic changes in breast milk melatonin throughout the course of lactation and to explore factors associated with changes in melatonin concentrations and rhythms in both preterm and term breast milk. Breast milk was collected sequentially at 03:00, 09:00, 15:00, and 21:00 in one day. Melatonin was analyzed in 392 breast milk samples from 98 healthy nursing mothers at 0 to 30 days postpartum. In both preterm and term breast milk, the melatonin concentration presented a circadian rhythm with the acrophase at around 03:00. Subgroup analysis showed the peak melatonin concentrations differed significantly across lactation stages, with the highest concentration in the colostrum, followed by transitional and mature breast milk. At 03:00, preterm breast milk had a higher concentration of melatonin than term breast milk in the colostrum (28.67 pg/mL vs. 25.31 pg/mL, p < 0.022), transitional breast milk (24.70 pg/mL vs. 22.55 pg/mL), and mature breast milk (22.37 pg/mL vs. 20.12 pg /mL). Further studies are warranted for their roles and significance on melatonin in breast milk in nutrition and metabolism of neonates.

Effects of personal air pollutant exposure on oxidative stress: Potential confounding by natural variation in melatonin levels.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) are commonly used biomarkers of oxidative stress. However, their associations with air pollutant exposure have not been consistent across studies. We hypothesize that the inconsistency is partly due to confounding of circulating melatonin. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), a surrogate of circulating melatonin, along with 8-OHdG and MDA, in 159 healthy adults who had not taken melatonin supplementation. Within the natural range of endogenously-generated aMT6s (0.3-93.5 ng/mg creatinine) measured in this study, increasing aMT6s levels were significantly associated with increasing concentrations of 8-OHdG and MDA. Measurements of PM2.5, ozone (O3), and nitrogen dioxide (NO2), coupled with time-activity data, were used to calculate time-averaged personal exposures 12 -hour (12h) and 24-hour (24h) prior to urine collection. Without controlling for aMT6s, the relationships between pollutant exposure and 8-OHdG or MDA were not clear. After controlling for aMT6s, an interquartile range (IQR) increase in 12h PM2.5 and 12h NO2 exposure was associated with 6.1% [95%CI: 1.6%-10.8%] and 8.6% [1.3%-16.5%] increase in MDA, respectively. An IQR increase in 12h O3 exposure was associated with a 5.7% [1.9%-9.7%] in 8-OHdG. The findings suggest the need for controlling for aMT6s as a confounder in using urinary 8-OHdG and MDA as biomarkers of oxidative stress related to short-term air pollution exposure.

Day-night behavior in river entry of kutum and its relation to melatonin

Reproduction in most fish species is a scheduled phenomenon and spawning occurs at a precise time ensuring maximum survival of offspring. During the spawning season, reproductive activities of fish species and their daily entry to rivers are influenced by environment. Number of Rutilus frisii kutum entered a river discharging to Caspian Sea was analyzed to investigate the association between timing of river entry and day–night changes in environmental variables. Four thousand five hundred and sixty seven ascending adult kutum were collected in Khoshkrood River between March and May 2012. Physicochemical parameters were recorded and Melatonin levels were measured in a hundred migratory kutum over day and night during the spawning period. A significant effect of daytime on river entry was observed, as more fish entered the river at night. Melatonin levels decreased to the minimum level during peak days of migration, suggesting variations in melatonin levels can help to harmonize the daily rhythm in kutum migration.

Determining diurnal and seasonal changes in melatonin andtryptophan contents of eggplant (Solanum melongena L.)

The objective of this study was to simultaneously determine changes in tryptophan and melatonin contents of eggplant seedlings at two different growth stages during a 24-h period. Variations in tryptophan and melatonin levels in different organs (roots, leaves, fruits, and seeds) and the distribution and accumulation of these molecules in these organs during various growth stages were also investigated. In eggplant seedlings, melatonin showed a strong peak at the beginning of the dark period, while tryptophan levels were at the lowest. Melatonin was also high in the middle of the light period and an inverse relationship was observed between melatonin and tryptophan levels. These results indicated that melatonin fluctuations in eggplant seedlings are likely the result of the combined effects of endogenous and environmental factors. Melatonin was found in high quantities in seedlings and mature seeds, and its concentration in leaves and roots decreased dramatically as the growth stages progressed. On the other hand, tryptophan content in leaves and roots increased markedly as the growth season progressed, and the highest tryptophan levels were detected in roots of older plants, flowers, and fruits at mature seed stage. Significant seasonal variations in melatonin levels suggest that melatonin may play a key role in eggplant developmental processes.

Contralateral Retinal Dopamine Decrease and Melatonin Increase in Progression of Hemiparkinsonium Rat

Both dopamine (DA) and melatonin (MLT) are abundant neuromodulators located in vertebrate retina. The retinal DA deficiency and variations in MLT levels have been linked to Parkinson's disease (PD). No studies have investigated the ipsilateral and contralateral DA and MLT in retina and their relationships in 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats. We established PD rat model by unilateral injection of 6-OHDA into the right substantia nigra and the right medial forebrain bundle. Eye tissue was collected and the levels of MLT and DA were measured twice daily at 10:00 and 22:00. The concentrations of DA and its metabolites, 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic acid (HVA), as well as MLT were determined by HPLC. The results show that DA levels in the eye contralateral to the side of a unilateral intracerebral 6-OHDA lesion significantly decreased (P < 0.001). Both the ratios of DOPAC/DA and HVA/DA were increased in comparison with the vehicle groups after 3 weeks post-lesion. The concentrations of MLT at 10:00 and 22:00 in both eyes were distinctly increased compared with the vehicle groups (P < 0.05). The change of DA and its metabolites, as well as MLT appeared to correlate well with the rotation behavior of rats. These findings suggest that rats receive a unilateral intracerebral injection of 6-OHDA that mainly causes the contralateral eye destruction of DA-containing neurons. Increased retinal MLT level probably is associated with the progression of PD.

Circulating Melatonin Levels: Possible Link Between Parkinson’s Disease and Cancer Risk?

Lower rates of cancer mortality/incidence in patients with Parkinson's disease (PD) have given rise to speculations about risk or preventative factors common to both diseases, including life-style factors (such as smoking) and genetic susceptibility. Melatonin, a hormone known for its sleep regulatory effects, may play an important role in carcinogenesis as suggested by substantial laboratory and less direct epidemiologic evidence. Particularly, a reduction in melatonin, such as experienced by persons who are exposed to light at night, appears to increase cancer risk. Variations in melatonin levels have been linked to PD in several different ways. Some studies show higher morning melatonin levels in PD patients than in healthy controls. One could speculate that the sleep disorders that affect almost two thirds of those suffering from PD and can precede PD motor symptoms by several years may be associated with variations in melatonin levels. Moreover, in animal models, interventions that increase the bioavailability of melatonin appears to increase the severity of parkinsonian symptoms, whereas reduction in melatonin by pinealectomy or exposure to bright light can enhance recovery from parkinsonisms symptoms. Finally, preliminary epidemiological evidence suggests that longer years of working night shifts is associated with a reduced risk of PD among participants of the Nurses' Health Study (NHS), whereas longer hours of sleep appear to increase their risk. In sum, while lower melatonin concentrations may predict a higher cancer risk, there is also some evidence that they may be associated with a lower risk of PD. We therefore hypothesize that elevated circulating melatonin levels in PD patients may contribute to their lower cancer rates.

Perinatal development of circadian melatonin production in domestic chicks.

In contrast to the situation in mammals, in which circadian melatonin production by the pineal gland does not begin until some time after birth, the development of pineal gland rhythmicity is an embryonic event in the precocial domestic fowl. A distinct melatonin rhythm was found in 19-d-old chick embryos maintained under light:dark (LD) 16:8. No significant variation in melatonin levels was detected in embryos exposed to LD 8:16. The melatonin rhythm in the pineal gland and plasma of chick embryos incubated for 18 d in LD 12:12 persisted for 2 d in constant darkness indicating that melatonin production is under circadian control at least from the end of embryonic life. A 1-d exposure to a LD cycle during the first postembryonic day was sufficient to entrain the melatonin rhythm, and previous embryonic exposure to either LD or constant darkness (DD) neither modified this rapid synchronization nor did it affect the melatonin pattern during the two subsequent days in DD. It is suggested that, in contrast to the situation in mammals, the avian embryo has evolved its own early circadian melatonin-producing system because, as a consequence of its extrauterine development, it cannot use the system of its mother.

Exposure of Female Rats to a 100-μT 50 Hz Magnetic Field Does Not Induce Consistent Changes in Nocturnal Levels of Melatonin

The hypothesis whereby alternating (50 or 60 Hz) magnetic fields such as those produced by electric power reduce the nocturnal production of melatonin in the pineal gland and thereby indirectly enhance development and growth of breast cancer has attracted a great deal of interest. In view of the potential importance of this hypothesis that there is a link between electric power and breast cancer, which is also known as the "melatonin hypothesis", we undertook various experiments in female Sprague-Dawley rats to evaluate whether 100-microT 50 Hz magnetic-field exposure, i.e. a flux density shown recently to exert a tumor (co)promoting effect in the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in Sprague-Dawley rats, consistently reduces melatonin levels and, if not, which factors may be involved in the inconsistent effects of magnetic-field exposure on production of melatonin. Long-term exposure of female Sprague-Dawley rats to magnetic fields for 13 weeks did not alter the nocturnal levels of melatonin in the pineal gland or serum (determined 5 h after the onset of darkness) significantly, irrespective of whether rats were treated with DMBA or not. In one experiment, when blood was sampled 3, 5 and 6 h after the onset of darkness after 2 weeks of magnetic-field or sham exposure, a significant decrease in melatonin was seen in magnetic-field-exposed rats at 6 h. However, the results could not be reproduced in two subsequent experiments in other groups of rats. Shorter (1 day, 1 week) or longer (4, 8, 13 weeks) exposure periods also did not result in any significant effects of the magnetic field on melatonin levels when blood sampling was performed either 5 or 6 h after onset of the dark phase. Various potential sources of variation in melatonin levels or in magnetic-field effects on melatonin levels were evaluated, but the reason(s) for the inconsistent effect of magnetic-field exposure remains unclear. Thus the present study failed to demonstrate a consistent effect of 100-microT 50 Hz magnetic-field exposure on melatonin levels in Sprague-Dawley rats.

Testosterone treatment alters melatonin concentrations in male patients with gonadotropin-releasing hormone deficiency.

Recently, we demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. As testosterone (T) can be aromatized to estradiol (E2), and both T and E2 increase during T enanthate treatment, we were interested in determining whether T treatment (when T and E2 levels were well matched with pubertal control values) has an effect on melatonin levels in these patients. We measured nocturnal serum melatonin levels during the administration of 250 mg testosterone enantale/month for 4 months in 12 male patients with idiopathic hypogonadotropic hypogonadism (IGD; n = 6) and delayed puberty (DP; n = 6). Serum samples for melatonin and LH determinations were obtained every 15 min from 1900-0700 h in a controlled light-dark environment. The results of melatonin profiles were compared with the pretreatment values in each group and with values obtained in six normal pubertal male controls. After 4 months of testosterone treatment, all patients attained normal serum testosterone (19.5 +/- 3.7 in IGD vs. 20.8 +/- 4.1 nmol/L in DP) and E2 levels (83 +/- 12 in IGD vs. 84 +/- 9 pmol/L in DP). Serum LH levels were suppressed in all patients during T treatment (0.12 +/- 0.1 in IGD vs. 0.12 +/- 0.2 IU/L in DP). Before T treatment, patient melatonin levels were greater than those in age-matched pubertal controls. Melatonin levels were equal in patients and controls when T and E2 levels were well matched. Mean (+/- SD) dark-time melatonin levels decreased from 286 +/- 23 to 157 +/- 36 pmol/L in IGD and from 217 +/- 32 to 133 +/- 47 pmol/L in DP (vs. 183 +/- 64 pmol/L in controls). The integrated melatonin values decreased to normal (from 184 +/- 16 to 102 +/- 21 in IGD and from 142 +/- 19 to 90 +/- 26 pmol/min.L x 10(3) in DP vs. 119 +/- 61 pmol/min.L x 10(3) in controls). The intraindividual variations in melatonin levels ranged from 7.2-14.5%. These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion. T treatment decreased melatonin secretion to normal levels. The results suggest that in GnRH-deficient male patients, sex steroids, rather than LH, modulate pineal melatonin in a reverse fashion.

Regional and diurnal studies of melatonin and melatonin binding sites in the duck gastro-intestinal tract.

Since melatonin and putative melatonin receptors can be detected in a variety of peripheral tissues, direct endocrine and paracrine actions of melatonin on the physiological functions of different organ systems in response to internal and external stimuli probably exist. As an extension of our earlier work on the pharmacological characterization of 2-[125I]iodomelatonin binding sites in the duck jejunum, the regional and diurnal variations of melatonin and putative melatonin receptors of different segments of the duck gastro-intestinal tract were studied in an attempt to understand the role of melatonin in the physiology of the digestive system. Although no significant effects of diurnal variation and pinealectomy on the regional distribution of melatonin were observed, significant regional variations of melatonin levels were detected with decreasing levels as follows: colon > oesophagus, caecum > duodenum, jejunum > ileum. The densities of melatonin binding sites showed a significant variation between different intestinal regions at either mid-light or mid-dark, with the following descending order: ileum, jejunum > duodenum, colon > caecum > oesophagus. Analysis of the distribution of melatonin binding sites in the wall of the intestine revealed maximal binding in the mucosa and minimal binding in the muscular layers of the jejunum. Similar results were obtained for other intestinal regions as revealed by autoradiography. No significant changes in the affinities of melatonin binding sites were detected between different regions and tissue layers of the alimentary canal. Moreover, the densities and affinities of melatonin binding sites among different regions of the gut exhibited no significant diurnal variations. The demonstration of regional variations in melatonin levels and the density of melatonin binding sites along the gastro-intestinal tract, with a concentration of the putative melatonin receptors in the mucosal layer, suggests a possible direct action of melatonin in the regulation of fluid/electrolyte transport and nutrient absorption in the gut.

Effects of photoperiod and different intensities of light exposure on melatonin levels in the blood, pineal organ, and retina of the brook trout (Salvelinus fontinalis Mitchill)

Daily variations in the melatonin concentration in the blood, pineal organ, and retina of the brook trout, Salvelinus fontinalis, were investigated in July under constant photoperiod (16 h L: 8 h D) and temperature (12 °C). Diel variations in melatonin levels in the blood and pineal organ showed similar patterns, with higher values during the night, whereas melatonin concentrations in the retina increased slightly in the first half of the light period. Light exposure of 1 h duration at mid-dark decreased melatonin levels in the blood and pineal organ in an intensity-dependent manner, whereas retinal melatonin levels increased with increasing light intensities. The minimum light intensity causing significant effects on the melatonin concentrations was 2 lx for the serum and 20 lx for the pineal organ and the retina. The parallelism between pineal and circulating melatonin patterns suggests that the lateral eyes of the trout have no significant endocrine function as far as the melatonin rhythm in the blood is concerned. Supporting evidence comes from the reversed response of retinal melatonin to light exposure at mid-dark, and from the low retinal melatonin concentrations found in this study. Thus, the serum melatonin rhythm of the brook trout seems to be mainly the result of rhythmic melatonin secretion from the pineal organ.

Inherited changes in concentrations of retinal and serum melatonin in the chicken

Concentrations of melatonin in the retina, serum, and pineal gland were studied in genetically blind chicks carrying an autosomal recessive mutation, rc, characterized by the degeneration of photoreceptors in the retina after hatching. Blind homozygous ( rc rc ) and sighted heterozygous ( Rc + rc ) chicks were housed under 12:12 light:dark cycles. They were decapitated at 4, 6, 8, and 10 weeks of age at midlight and middark. Retinas, pineal glands, and serum samples were collected, and the resultant tissue melatonin was extracted and determined by radioimmunoassay. Retinal and pineal melatonin were also identified and quantified by gas chromatography-mass spectrometry (GC-MS). Good correlations were demonstrated between the values obtained by GC-MS and levels quantified by radioimmunoassay. In all the tissues studied, there were age-related changes and diurnal variations in melatonin levels with high levels in the dark period. Melatonin levels in the retina and serum of rc rc chicks were also significantly lower than those of Rc + rc control birds. However, storages of melatonin in the pineal gland were similar between the two groups of chicks studied. These results suggest that (1) retinal melatonin is synthesized in the photoreceptor, (2) the phototransduction process which produces neural signals (i.e., electroretinogram) may be different from the phototransduction process which initiated the rhythmic melatonin synthesis and production in the retina, (3) the inherited degeneration of retinal photoreceptors with lower retinal melatonin levels correlates with an inherited abnormality of the pineal melatonin synthesis and/or secretion resulting in lower serum melatonin levels (pleiotropism), (4) levels of pineal melatonin (an indicator of the rate of synthesis and/or storage) and that of serum melatonin (an indicator of the rate of release) may not be directly correlated, and (5) the chicken pineal secretes melatonin not only by simple diffusion but also from a bound pool of melatonin in the gland.

Circadian variations in the inhibition of dopamine release from adult and newborn rat hypothalamus by melatonin.

The inhibitory effect of melatonin on evoked dopamine release from the hypothalamus was studied in adult male rats throughout a 24-hour period. The animals were maintained under a daily schedule of 14 h of light (0.00-14.00 h) and 10 h of darkness. The inhibition of dopamine release in vitro by 1 microM melatonin clearly exhibited a 24-hour rhythm with a peak at 5.00 h and almost no inhibition at 15.00 h. The concentrations of melatonin needed to produce this effect were similar throughout the 24-hour cycle, although the actual amount of inhibition at any given concentration of melatonin varied. Other indole derivatives, with the exception of 5-methoxy tryptophol, did not affect significantly the release of 3H-dopamine from the male rat hypothalami. The inhibition of dopamine release by melatonin was not observed in newborn rats but developed during the first week of life, reaching a plateau level between 6 and 7 days postnatally. However, the difference between the amount of inhibition by melatonin at 5.00 h and at 8.00 h existed from the time the inhibition was first observed. The change in amplitude of this difference was due not to differences in the apparent affinity towards melatonin but to increase in the maximal inhibition observed at 5.00 h. The data indicate that the hypothalamic sensitivity to melatonin exhibits a circadian rhythm, and that this develops postnatally prior to the development of circadian variations in melatonin levels, i.e. the 'melatonin rhythm'.(ABSTRACT TRUNCATED AT 250 WORDS)