Changes In Melatonin Concentrations Research Articles

Melatonin in Human Breast Milk and Its Potential Role in Circadian Entrainment: A Nod towards Chrononutrition?

Breastfeeding is the most appropriate source of a newborn’s nutrition; among the plethora of its benefits, its modulation of circadian rhythmicity with melatonin as a potential neuroendocrine transducer has gained increasing interest. Transplacental transfer assures melatonin provision for the fetus, who is devoid of melatonin secretion. Even after birth, the neonatal pineal gland is not able to produce melatonin rhythmically for several months (with an even more prolonged deficiency following preterm birth). In this context, human breast milk constitutes the main natural source of melatonin: diurnal dynamic changes, an acrophase early after midnight, and changes in melatonin concentrations according to gestational age and during the different stages of lactation have been reported. Understudied thus far are the factors impacting on (changes in) melatonin content in human breast milk and their clinical significance in chronobiological adherence in the neonate: maternal as well as environmental aspects have to be investigated in more detail to guide nursing mothers in optimal feeding schedules which probably means a synchronized instead of mistimed feeding practice. This review aims to be thought-provoking regarding the critical role of melatonin in chrononutrition during breastfeeding, highlighting its potential in circadian entrainment and therefore optimizing (neuro)developmental outcomes in the neonatal setting.

Sleep disorders and changes in melatonin concentrations in pregnant women with preeclampsia

Melatonin plays a significant role in the development of normal pregnancy, in particular, it contributes to the successful implantation of the fertilized egg, affects the act of childbirth, is actively produced by the trophoblast and placenta, reduces oxidative stress, in particular, with preeclampsia. In addition, melatonin is one of the essential hormones in the protection of the endothelium and stem cells from the oxidant stress. Objective – to study the mechanisms of development, terms of manifestation, and types of sleep disorders, as well as changes in the concentrations of melatonin in the blood of pregnant women with preeclampsia. Material and methods. 50 pregnant women at a mean age of 29.1±3.4 years who had preeclampsia in the 3rd pregnancy trimester were examined (experimental group). All women in the research group had a gestation term of 30-32 weeks of pregnancy. The control group consisted of 33 women with a mean age of 31.2±6.6 years who had an uncomplicated pregnancy. The presence of sleep disorders was established using a questionnaire: pregnant women were asked about the term of pregnancy in which complaints of sleep disorders appeared, the nature of sleep disorders, the frequency of episodes of sleep disorders (how many times a week such a condition was noted), etc. The concentration of melatonin in the venous blood of the examined pregnant women was also determined, for which IBL melatonin ELISA diagnostic kits manufactured by IBL, Germany were used. Blood was taken at 9:00 a.m., on an empty stomach, and all patients were analyzed at the same time of a day. Results and their discussion. The study showed that sleep disorders in pregnant women with pre-eclampsia, which complicates the pregnancy in the 3rd trimester, occurred earlier, compared to women with an uncomplicated course of pregnancy: pregnant women with pre-eclampsia were more likely to notice worsening of sleep, starting from 22-30 weeks of pregnancy (in 26.0 % of cases), while in pregnant women with a physiological course of gestation, similar complaints appeared mainly after 30 weeks. In the third trimester of pregnancy women with preeclampsia were more likely to wake up 2 or more times per night (in 68.0 % of cases) compared to controls (in 23.3 % of cases, p < 0.001) and 3 or more times per night per week (in 54.0 % of cases, in controls – in 16.7 % of cases, p < 0.001), which may be a consequence of a disorder of the function of the pineal gland. Women with preeclampsia were more likely (56.0 % vs. 13.3 % in the control group, p < 0.01) to use gadgets (electronic devices, mainly smartphones) for more than 2 hours after 9:00 p.m., which also negatively affects the function of the pineal gland. In pregnant women whose pregnancy was complicated by preeclampsia in the 3rd trimester, a significant (1.78-fold) decrease in the level of melatonin in venous blood taken at 9 a.m. was observed, compared to women with an uncomplicated pregnancy (p = 0.029). Conclusions. Sleep disorders in pregnant women with preeclampsia occur earlier and are more expressed compared to women with an uncomplicated course of pregnancy. The appearance of complaints of insomnia in the second trimester of pregnancy, in our opinion, can be considered a diagnostic sign of pineal gland dysfunction in preeclampsia. A decrease in the level of melatonin in pregnant women with preeclampsia, established against the background of minimal daily activity of the pineal gland (at 9 a.m.), indicates a decrease in the melatonin-producing function of the placenta which might have an impact on the condition of stem cells of fetus and placenta.

Changes in Melatonin Concentration in a Clinical Observation Study under the Influence of Low-Frequency Magnetic Fields (Magnetic Stimulation in Men with Low Back Pain)-Results of Changes in an Eight-Point Circadian Profile.

The aim of this study was to assess the changes in melatonin concentration under the influence of magnetic stimulation in men with low back pain. A total of 15 men were used in this study, divided into two groups. In Group 1, consisting of seven men, the M1P1 Viofor JPS program was used twice a day for 8 min, at 08:00 and 13:00. In Group 2, consisting of eight men, the M2P2 Viofor JPS program was used once a day for 12 min at 10:00. The application was subjected to the whole body of patients. The treatments in both groups lasted 3 weeks, for 5 days each week, with breaks on weekends. The diurnal melatonin profile was determined the day before exposure and the day after the last treatment, as well as at one-month follow-up. Blood samples were collected eight times a day. In both programs, magnetic stimulation did not reduce the nocturnal peak of melatonin concentration. After exposure, prolonged secretion of melatonin was observed until the morning hours. The impact of the magnetic field was maintained 1 month after the end of the application. The effect of the magnetic field was maintained for 1 month from the end of the application, which confirms the thesis about the occurrence of the phenomenon of biological hysteresis. The parameters of the magnetic fields, the application system, and the time and length of the application may affect the secretion of melatonin.

Changes in concentrations of melatonin, PlGF, and cytokines in women with preeclampsia.

Preeclampsia (PE) is a pregnancy-related disorder that significantly increases the risk of maternal and fetal morbidity and mortality. Melatonin, a potent antioxidant, has been suggested to mitigate oxidative stress and associated damage in various pathological conditions. Placental growth factor (PlGF) plays a vital role in placental development by promoting angiogenesis. This study aimed to investigate whether the levels of melatonin, cytokines, and PlGF were higher in the venous blood of women with preeclampsia during the third trimester of pregnancy compared to those with uncomplicated pregnancies. The study involved 32 women with preeclampsia and 33 healthy pregnant women as a control group. The concentrations of melatonin and PlGF were significantly lower in women with preeclampsia compared to healthy pregnant women. Specifically, the mean level of melatonin in the preeclampsia group was 30.98 pg/ml and 55.20 pg/ml in the control group (p=0.029). Similarly, the mean level of PlGF in the preeclampsia group was 40.03 pg/ml and 213.31 pg/ml in the control group (p<0.0001). This suggests that alterations in the placental production of melatonin and PlGF may contribute to the development of preeclampsia. In contrast, we observed higher levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) in the preeclampsia group than in the control group. The mean concentration of IL-6 in the PE group was 270.79 pg/ml, whereas the control group had 224.30 pg/ml (p=0.022). Similarly, the mean concentration of IL-10 in the PE group was 41.90 pg/ml and 30.73 pg/ml in the control group (p=0.018). In women with uncomplicated pregnancies, the interaction between pro-inflammatory interleukine-6 and melatonin can be described by equality of statistical regression.

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.

Concentrations of melatonin, thyroxine, 17β-estradiol and 11-ketotestosterone in round goby (Neogobius melanostomus) in different phases of the reproductive cycle

The aim of this study was to determine changes in concentrations of melatonin (Mel) and thyroxine (T4) in plasma, and 17β-estradiol (E2) and 11-ketotestosterone (11-KT) in plasma and gonads of female and male round gobies (Neogobius melanostomus) from the Southern Baltic Sea in four phases of the reproductive cycle classified as pre-spawning, spawning, late spawning and non-spawning periods. The concentrations of Mel, T4 and E2 were determined by radioimmunoassay (RIA) whereas 11-KT was quantified using an enzyme immunoassay (EIA). The maturity stage of gonads was determined using histological analyses. The pattern of changes in Mel concentrations of females and males was similar with the greatest concentrations in the spawning and non-spawning phases. In both sexes, there was a similar tendency of change in concentrations of T4 and E2 with the increase being in the pre-spawning and non-spawning phases. The greatest concentrations of 11-KT were observed in the plasma and gonads of males during the spawning phase. In females, there were no changes in 11-KT concentrations either in plasma or gonads during all phases where quantifications occurred. This is the first study for determination of the pattern of changes in Mel and T4 concentrations as well as gonadal steroids E2 and 11-KT, supported by histological analysis of gonads, in batch spawning fish during the reproductive cycle.

Changes in melatonin concentrations in seminal plasma are not correlated with testosterone or antioxidant enzyme activity when rams are located in areas with an equatorial photoperiod

In temperate climates, photoperiod and melatonin regulate ram reproduction, modulating hormonal secretions, sperm quality, and seminal plasma composition. Information on the effect of an equatorial photoperiod (12L:12D) on ram reproduction, however, is scarce, and no data on hormonal concentrations and antioxidant enzyme activity in seminal plasma have been reported. Thus, the variation was investigated of melatonin and its relationship with testosterone and antioxidant enzyme activity in the seminal plasma of three sheep breeds in Colombia, when there was a consistent photoperiod during two dry and two rainy seasons per year. Semen was collected once a week from 12 mature rams (four of each breed: Colombian Creole, Hampshire, and Romney Marsh). Seminal plasma was obtained by centrifugation. The concentration of melatonin and testosterone were quantified along with the enzymatic activity of glutathione peroxidase (GPx), glutathione reductase (GRD), and catalase (CAT). Correlation analyses between melatonin and testosterone concentrations or enzymatic activity were also performed. Melatonin concentration was affected by season (P < 0.05) but not breed, with lesser concentrations in the first rainy season. Testosterone concentration, however, was affected by breed and season, with greater concentrations (P < 0.01) in the Hampshire and Romney Marsh rams during the second dry season. Regarding antioxidant enzyme activity, there was only seasonal variation in GPx activity (P < 0.05). When correlation analyses were used for data assessments, there was a negative correlation between melatonin and testosterone concentrations in Hampshire rams. In conclusion, melatonin concentrations in seminal plasma of rams that were located in an area with an equatorial photoperiod was affected by the climatological season but there was no positive correlation with testosterone concentration or antioxidant enzyme activity.

Applying Melanopic Lux to Measure Biological Light Effects on Melatonin Suppression and Subjective Sleepiness

At the beginning of this century, a novel photopigment, melanopsin, was discovered in a sub-class of retinal ganglion cells and its action spectrum was described. Shortly after, it became evident that melanopsin is a major contributor to non-visual eye-mediated effects of light on e.g. the circadian, neuroendocrine and neurobehavioral systems. First applied studies pointed out that these non-visual effects of light are relevant for wellbeing, performance and general health. A standardized measurement metric for these nonvisual effects does not exist, but would ease application. Such a metric termed as 'melanopic lux' has been recently introduced and was shown to be superior to describe non-visual effects in animal studies compared to standard metrics. We aimed at showing some validity of melanopic lux in humans using a seminaturalistic setting. Therefore, we analyzed the impact of different lighting conditions on melatonin suppression and subjective sleepiness by calculating effective illuminance based on single photopigment sensitivities. We retrospectively analyzed data from our laboratory, where young participants were exposed to a total of 19 different polychromatic lighting conditions, for 30 minutes in the evening, one hour prior to habitual bedtime. Saliva samples for melatonin concentration measures and subjective sleepiness were regularly assessed. The photopic illuminance of all lighting conditions ranged from 3 to 604 lx. Stepwise for- and backward regression analyses showed that melanopic lux was the best predictor for changes in melatonin concentrations (but not subjective sleepiness); R²=0.16 (p<0.05). In addition, we found a significant dose-response relationship between melanopic lux and changes in melatonin concentrations for 18 different lighting conditions (adjusted R²=0.52; p=0.004), similarly to what was previously reported for photopic lux. Our results indicate some new relevance for the application of melanopic lux as an additional metric to predict non-visual light effects of electrical light sources for nursing homes, work places, and homes.

Shift work and endocrine disorders.

The objective of this review was to investigate the impact of shift and night work on metabolic processes and the role of alterations in the sleep-wake cycle and feeding times and environmental changes in the occurrence of metabolic disorders. The literature review was performed by searching three electronic databases for relevant studies published in the last 10 years. The methodological quality of each study was assessed, and best-evidence synthesis was applied to draw conclusions. The literature has shown changes in concentrations of melatonin, cortisol, ghrelin, and leptin among shift workers. Melatonin has been implicated for its role in the synthesis and action of insulin. The action of this hormone also regulates the expression of transporter glucose type 4 or triggers phosphorylation of the insulin receptor. Therefore, a reduction in melatonin can be associated with an increase in insulin resistance and a propensity for the development of diabetes. Moreover, shift work can negatively affect sleep and contribute to sedentarism, unhealthy eating habits, and stress. Recent studies on metabolic processes have increasingly revealed their complexity. Physiological changes induced in workers who invert their activity-rest cycle to fulfill work hours include disruptions in metabolic processes.

Influence of melatonin receptor 1A gene polymorphisms on seasonal reproduction in Sarda ewes with different body condition scores and ages

In several species, circadian changes in melatonin concentrations play a key role in the photoperiodic control of seasonality. In sheep, two silent mutations in the melatonin receptor 1A gene (MTNR1A) at positions 606 and 612 of the exon II are associated with seasonal reproduction. However, in some sheep breeds, no relationships have been found between MTNR1A polymorphisms and reproductive seasonality. This lack of relationship could be due to effects of breed, body condition, age, and/or environmental conditions. Thus, the present study was conducted with the Sarda sheep breed with the aim of documenting the effect of MTNR1A gene polymorphisms on reproductive resumption and to evaluate whether such this effect was modified by differences in body condition score (BCS) and age. Six hundred three- to six-year-old multiparous ewes with BCSs between 2.5 and 3.5 were selected. Genomic DNA was extracted and subjected to PCR to amplify the ovine exon II of the MTNR1A gene. The amplicons were subjected to digestion with the restriction enzymes RsaI and MnlI to detect the T606C and A612G polymorphisms, respectively. Ewes carrying the G/G, G/A, C/C, and C/T genotypes exhibited higher fertility rates (P<0.05) and fewer numbers of days between the introduction of rams and parturition (P<0.05) than did the A/A and T/T genotypes. The data revealed that the MTNR1A gene polymorphisms influenced spring reproductive resumption in the Sarda sheep breed. Moreover, the data also indicated that, over the limited ranges evaluated in this study, BCS and age had no significant influence on reproductive activity.

Melatonin in perimenopausal and postmenopausal women

Melatonin synthesis and secretion are partly modulated by estrogen and progesterone. Changes in melatonin concentrations, possibly related to the menopausal transition, may be associated with climacteric mood, sleep, and vasomotor symptoms. The aims of this study were to compare the serum concentrations of melatonin in perimenopausal and postmenopausal women and to evaluate melatonin's influence on mood, sleep, vasomotor symptoms, and quality of life. We analyzed the data of 17 healthy perimenopausal women (aged 43-51 y) and 18 healthy postmenopausal women (aged 58-71 y) who participated in a prospective study. On study night (9:00 pm-9:00 am), serum melatonin was sampled at 20-minute (9:00 pm-12:00 midnight; 6:00-9:00 am) and 1-hour (12:00 midnight-6:00 am) intervals. Questionnaires were used to assess depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), insomnia and sleepiness (Basic Nordic Sleep Questionnaire [BNSQ]), subjective sleep quality, vasomotor symptoms, and quality of life (EuroQoL). Postmenopausal women had lower nighttime serum melatonin concentrations than perimenopausal women. The duration of melatonin secretion tended to be shorter in postmenopause, whereas melatonin peak time did not differ. Mean melatonin concentrations and exposure levels did not correlate with follicle-stimulating hormone level, estradiol level, body mass index, Beck Depression Inventory score, State-Trait Anxiety Inventory score, BNSQ insomnia score, BNSQ sleepiness score, subjective sleep score, climacteric vasomotor score, or quality of life. In perimenopause, the later is the melatonin peak, the higher is the level of anxiety (P = 0.022), and the longer is the melatonin secretion, the better is the quality of life (P < 0.001). Longitudinal research is needed to better understand the possible contributory role of menopause in lower melatonin levels.

Temporal and histological evaluation of melatonin patterns in a ‘basal’ metazoan

While recent advances suggest functional pleiotropy of melatonin in higher organisms, an understanding of the biological significance of this ancient molecule in early evolutionary groups is lacking. Here, endogenous melatonin production was identified for the first time in the sea anemone Actinia equina, a nonsymbiotic hexacorallian cnidarian. Day/night activity profiles of melatonin in this anemone indicated that melatonin levels oscillate with significant nocturnal peaks. However, dynamic changes in melatonin concentration did not persist under constant dark conditions and therefore were not circadian in nature. Thus, the oscillating pattern of melatonin in A.equina is presumed to be the result of alternative, simpler melatonin control mechanism that likely involves direct regulation by the daily photocycle. As nocturnal melatonin signals still potentially provide 'time-of-day' information and can illustrate the seasonally changing length of the biological night, we hypothesize that melatonin may be relevant to temporal coordination of timed processes also in anthozoans. Spatial patterns of melatonin distribution found in this study indicate abundant melatonin distribution in the endodermal filaments wrapped around gametes. This finding supports the possibility that one of the melatonin-responsive processes in this basal metazoan species may involve reproductive functions.

Malaria: therapeutic implications of melatonin

Malaria, which infects more than 300 million people annually, is a serious disease. Epidemiological surveys indicate that of those who are affected, malaria will claim the lives of more than one million individuals, mostly children. There is evidence that the synchronous maturation of Plasmodium falciparum, the parasite that causes a severe form of malaria in humans and Plasmodium chabaudi, responsible for rodent malaria, could be linked to circadian changes in melatonin concentration. In vitro melatonin stimulates the growth and development of P. falciparum through the activation of specific melatonin receptors coupled to phospholipase-C activation and the concomitant increase of intracellular Ca2+. The Ca2+ signaling pathway is important to stimulate parasite transition from the trophozoite to the schizont stage, the final stage of intraerythrocytic cycle, thus promoting the rise of parasitemia. Either pinealectomy or the administration of the melatonin receptor blocking agent luzindole desynchronizes the parasitic cell cycle. Therefore, the use of melatonin antagonists could be a novel therapeutic approach for controlling the disease. On the other hand, the complexity of melatonin's action in malaria is underscored by the demonstration that treatment with high doses of melatonin is actually beneficial for inhibiting apoptosis and liver damage resulting from the oxidative stress in malaria. The possibility that the coordinated administration of melatonin antagonists (to impair the melatonin signal that synchronizes P. falciparum) and of melatonin in doses high enough to decrease oxidative damage could be a novel approach in malaria treatment is discussed.

Immunohistochemical definition of MT 2 receptors and melatonin in the gastrointestinal tissues of rat

The gastrointestinal tract of vertebrate species contains melatonin, which participates in several physiological functions. Some of these effects are mediated via specific membrane receptors (MT(1) and MT(2)). In the present study, the distribution of the MT(2) receptor protein in the gastrointestinal tract was localized, and changes in MT(2) receptor density were observed in relation to the expected circadian changes in melatonin concentrations. Immunohistochemistry was performed in the rat stomach, duodenum, colon and pancreas. The amount of MT(2) was determined by Western blot. Melatonin concentrations were measured by radioimmunoassay (RIA). In the stomach, duodenum and colon, the most intense immunoreactivity was observed in the Muscularis mucosae and in the Muscularis externa. In the pancreas, the immunolabelling was less intense. There was a clear daily rhythm of melatonin concentrations in the stomach, duodenum and pancreas, with higher levels during the dark period. The density of MT(2) receptors did not exhibit circadian variation. Moreover, circadian changes in melatonin concentrations were not found in the colon. The density of MT(2) was the highest in the colon. Our results provide evidence for the heterogeneous distribution of MT(2) receptors in different parts and layers of the gastrointestinal tract, which could indicate a physiological role of melatonin in the gastrointestinal tract.

Serum melatonin circadian profiles in women suffering from cervical cancer

Although there is an increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore, we decided to study the circadian melatonin rhythm in patients suffering from cervical cancer in different stages of progression and to compare them with those in subjects free from neoplastic disease. A total of 45 women were analyzed in this study. The subjects were divided into two groups. The first group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer in various stages of the disease. The second group consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.), range 42-63] who served as the control group. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration was measured by immunoenzymatic method. There were significant differences in circadian melatonin profiles as well as in the area under curve among the two studied groups. Melatonin concentrations were significantly lower in cancer patients in comparison with healthy individuals. Taking into consideration stage of the cervical cancer significantly lower melatonin secretion has been found in all subgroups of patients in comparison with that of tumor-free control group. Additionally, nocturnal melatonin concentrations as well as area under curve were significantly lower in advanced stage of cancer (stages 3 and 4) in comparison with patients with preinvasive cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1 disease at 02:00 and 04:00 hours. The results of the present study indicate that the presence of cervical cancer influences melatonin levels in women. Moreover, stage dependence in reduction of melatonin concentrations has been found.

The expression of MT 1 and MT 2 melatonin receptor mRNA in several rat tissues

The mechanisms that mediate the various effects of melatonin in mammalian tissues are not always known. Therefore, the aim of this study was to investigate whether MT 1 and MT 2 melatonin receptors are expressed in certain tissues of the rat. The expression of MT 1 and MT 2 melatonin receptor mRNA was determined using a real-time quantitative RT-PCR method. In addition, we examined whether mRNA for either subtype of receptor shows any difference in the expression between midnight and noon, similar to the changes in melatonin concentrations in plasma and tissue samples. MT 1 and MT 2 melatonin receptor mRNAs were found in the rat hypothalamus, retina and small intestine. We also showed a low expression of MT 2 mRNA in the rat liver and heart SA node. In the heart apex and the Harderian gland, no appearance of either of the receptor mRNAs was detectable. A significant difference in the expression of MT 1 mRNA between day and night was found in the hypothalamus. In conclusion, our findings suggest that at least some effects of melatonin are mediated through membrane MT 1 and MT 2 receptors in the hypothalamus, the retina and the small intestine. Down-regulation of receptors might be one reason for the difference in the hypothalamic MT 1 melatonin receptor mRNA expression between midnight and noon. In the liver and the heart SA node, the physiological significance of possible MT 2 receptors remains unclear. According to our negative midnight and noon results in the Harderian gland and heart apex melatonin may exert its effect on these tissues by a non-receptor mechanism.

Changes in estradiol, progesterone, melatonin, prolactin and thyroxine concentrations in blood plasma of goats following induced estrus in and outside the natural breeding season

The aim of this trail was to determine and compare the profiles of changes in progesterone (P4), 17-β-estradiol (E2), melatonin (MEL), prolactin (PRL) and free thyroxine (FT4) in the peripheral blood following induced estrus in and outside the natural breeding season in goats. Observations were made on Anglo-Nubian does in the autumn (n=12) and spring (n=12). Does were treated with intravaginal progestagen sponges (40mg FGA) for 12 days, and 500IU PMSG i.m. at sponge withdrawal whereafter blood samples were collected. Samples were collected from 24 to 68h following sponge withdrawal and the occurrence of estrous symptoms was recorded.Estrus occurred in both groups (season) of animals. However, in autumn (breeding season) estrus occurred earlier and persisted longer than in spring (outside the breeding season). Also in autumn plasma concentration of progesterone (0.42±0.11 versus 0.27±0.08ng/ml; P<0.01) and estradiol (15.3±5.0 versus 12.2±3.8pg/ml; P<0.01) were higher. Moreover, in autumn significant differences in MEL concentration were recorded at night, 16:00 and 06:00h, between the first (30–44h after sponge withdrawal) and the second dark phase (54–68h after sponge withdrawal) (22.5±16.8 versus 70.1±27.0pg/ml; P<0.01). Time was found to have a negative correlation between changes in concentrations of MEL and E2 (r=−0.33; P<0.01) and between MEL and FT4 (r=−0.39; P<0.01). In spring these correlations were positive and the differences between MEL concentration at night (18:00 and 04:00h) in the first (34–42h after sponge withdrawal) and the second dark phase (58–66h after sponge withdrawal) were not significant (46.3±9.3 and 46.5±11.3pg/ml, respectively). In all does an increase of PRL concentration was recorded, several times higher than the basal one, which occurred a few hours earlier in autumn than in spring. In spring mean PRL concentration was higher than in autumn (103.0±58.7 versus 23.0±20.3ng/ml, respectively; P<0.01). Similar differences that refer to FT4 concentration (spring 14.4±4.1 versus autumn 8.9±2.3pg/ml, respectively; P<0.01) were recorded. In conclusion, the results show seasonal differences in the secretion of the ovarian steroid hormones, melatonin and thyroxine, following induced estrus, which suggests a different reproduction capacity in the two seasons. Seasonal differences in the profile of melatonin release during estrus may be related to the estradiol and thyroxine secretions.

Seasonal changes in melatonin concentrations in female Iberian red deer (Cervus elaphus hispanicus).

In deer, most of the earlier investigations on pineal function examined the effects of artificial photoperiods or the administration of melatonin to manipulate reproduction. However, endogenous melatonin rhythms have not been studied in red deer. Thus, we monitored seasonal changes in plasma melatonin concentrations in 16 adult female Iberian red deer living in outdoor enclosures. Blood was sampled on the day of each seasonal change every 3-4 hr overnight and 1 hr before and after sunset and sunrise. In addition, in six of the previous hinds, blood sampling during the hour prior and after sunset and sunrise was collected every 20 min. Significant differences were found both in amplitude and duration of the nocturnal plasma melatonin profiles in the four seasonal changes (P < 0.01). The nocturnal mean level of melatonin, the duration of nocturnal secretion levels and maximal concentrations were significantly higher at the winter solstice than in summer solstice or equinoxes (P < 0.05). Moreover, the mean overnight concentrations were significantly higher at the spring equinox and winter solstice than during the summer solstice and autumn equinox (P < 0.05). A pronounced elevation from low levels was recorded 1 hr after sunset, remained elevated during the hours of darkness and declined to low levels 1 hr after dawn. Concentrations close to sunrise were higher than those near sunset at all changes of season (P < 0.05). These results show for the first time in red deer that the pineal gland of the adult female is highly responsive to both daily and seasonal changes in natural environmental illumination, although overnight levels lasted longer than the photoperiodic night is all cases, particularly at the winter solstice.

The relevance of melatonin to sports medicine and science.

The pineal hormone, melatonin, has widespread effects on the body. The aim of this review is to consider the specific interactions between melatonin and human physiological functions associated with sport and exercise medicine. Separate researchers have reported that melatonin concentrations increase, decrease and remain unaffected by bouts of exercise. Such conflicting findings may be explained by inter-study differences in lighting conditions and the time of day the study participants have exercised. Age and fitness status have also been identified as intervening factors in exercise-mediated changes in melatonin concentration. The administration of exogenous melatonin leads to hypnotic and hypothermic responses in humans, which can be linked to immediate reductions in short-term mental and physical performance. Depending on the dose of melatonin, these effects may still be apparent 3-5 hours after administration for some types of cognitive performance, but effects on physical performance seem more short-lived. The hypothesis that the hypothermic effects of melatonin lead to improved endurance performance in hot environments is not supported by evidence from studies involving military recruits who exercised at relatively low intensities. Nevertheless, no research group has examined such a hypothesis with athletes as study participants and with the associated more intense levels of exercise. The fact that melatonin has also been found to preserve muscle and liver glycogen in exercised rats adds weight to the notion that melatonin might affect endurance exercise in humans. Melatonin has been successfully used to alleviate jet lag symptoms of travellers and there is also a smaller amount of evidence that the hormone helps shiftworkers adjust to nocturnal regimens. Nevertheless, the symptoms of jet lag and shiftwork problems have primarily included sleep characteristics rather than performance variables. The few studies that have involved athletes and performance-related symptoms have produced equivocal results. Melatonin has also been found to be useful for treating some sleeping disorders, but interactions between sleep, melatonin and exercise have not been studied extensively with trained study participants. It is unknown whether melatonin plays a role in some exercise training-related problems such as amenorrhoea and over-training syndrome.

Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster.

The purpose of these studies was to investigate the effects of melatonin on the production of steroids (progesterone, testosterone, and estradiol) and cAMP by preovulatory follicles and to examine changes in melatonin concentrations in the ovary during the estrous cycle. Adult cyclic hamsters were used in this study. Melatonin concentrations in the ovary, pineal gland, and serum were measured at mid-light and mid-dark during the estrous cycle. Effects of melatonin on steroidogenesis by preovulatory follicles, thecae, and granulosa cells were examined, and its effect on cAMP production by preovulatory follicles was also investigated. Melatonin (0.1-10 ng/ml) had no effect on steroid production in the absence of hCG, but melatonin decreased progesterone and estradiol production by preovulatory follicles in a dose-dependent and time-dependent manner in the presence of hCG (100 mIU/ml). The target of melatonin was thecae but not granulosa cells, and melatonin significantly reduced cAMP production by preovulatory follicles. Melatonin concentrations in the ovary showed a similar phasic variation with high levels during mid-dark and low during mid-light, as in the pineal gland and serum. These results show that the ovarian melatonin levels also exhibit a circadian rhythm and suggest that the high melatonin milieu in the ovary may induce gonadal regression in the cyclic hamster.