Abstract
Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides being produced in peripheral tissues and acting as an autocrine and ...paracrine signal, melatonin is centrally synthetized by a neuroendocrine organ, the pineal gland. Independently of the considered species, pineal hormone melatonin is always produced during the night and its production and secretory episode duration are directly dependent on the length of the night. As its production is tightly linked to the light/dark cycle, melatonin main hormonal systemic integrative action is to coordinate behavioral and physiological adaptations to the environmental geophysical day and season. The circadian signal is dependent on its daily production regularity, on the contrast between day and night concentrations, and on specially developed ways of action. During its daily secretory episode, melatonin coordinates the night adaptive physiology through immediate effects and primes the day adaptive responses through prospective effects that will only appear at daytime, when melatonin is absent. Similarly, the annual history of the daily melatonin secretory episode duration primes the central nervous/endocrine system to the seasons to come. Remarkably, maternal melatonin programs the fetuses' behavior and physiology to cope with the environmental light/dark cycle and season after birth. These unique ways of action turn melatonin into a biological time-domain-acting molecule. The present review focuses on the above considerations, proposes a putative classification of clinical melatonin dysfunctions, and discusses general guidelines to the therapeutic use of melatonin.
Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, ...particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.
The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate ...susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (
).
Eight SNPs in
were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated.
The group of individuals with a renal function decline ≥ 5 mL min
1.73 m
year
presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82;
= 0.0046). No other significant associations were found.
This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.
The emergence of the coronavirus disease 2019 (COVID-19) pandemic and subsequent lockdowns and social distancing measures adopted worldwide raised questions about the possible health effects of human ...social isolation.
We conducted a systematic review on PubMed, Scopus, and Embase electronic databases using terms related to human social isolation - defined as the isolation of an individual from regular routines and usual social contact - and psychological stress, searching for simulated or naturalistic isolation environments. We present the main results, as well as the validity and limitations of each model. PROSPERO registry number: CRD42021241880.
Despite the diversity of contexts reviewed, some outcomes almost ubiquitously relate to psychological stress, i.e., longer periods, expectation of a longer period, confinement, lack of social interaction, and support. Based on the results, and considering that most studies were not designed for the purpose of understanding isolation itself, we propose a group of recommendations for future experimental or naturalistic research on the topic.
Evidence on the impact of different situations in which individuals are subjected to social isolation can assist in development of directed preventive strategies to support people under similar circumstances. Such strategies might increase the general public's compliance with social distancing as a non-pharmacological intervention for emerging infectious diseases.
•Melatonin regulates male and female reproductive systems.•Maternal melatonin blood levels increase during gestation.•Melatonin regulates maternal physiological adaptations to pregnancy and ...lactation.•The fetus depends on maternal melatonin, that crosses the placenta.•Melatonin regulates fetal development and programming of physiological functions.
Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism’s physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.
ABSTRACT Objectives: to compare the parameters of the activity/rest cycle of early postpartum breastfeeding women under a controlled and uncontrolled long wavelength ray light regimen. Methods: ...quasi-experimental study with breastfeeding women and their babies during postnatal rooming-in, São Paulo, Brazil. Participants were allocated to either an experimental (intervention) or a comparison group. The intervention involved exposure of the woman in a controlled room with artificial long wavelength ray light at night. Each woman’s level of 6-sulfatoxymelatonin at 24 hours and activity/rest times was analyzed. Results: the mean activity/rest times of women in the experimental and comparison groups were similar. The mean percentages of total load of 6-sulfatoxymelatonin during the day and night were similar (p=0.09). At 24 hours, the experimental group presented a significantly lower mean percentage of total load compared to the comparison group (p=0.04). Conclusions: women who stayed in the room with long-wavelength artificial light showed no difference in activity/rest and 6-sulfatoxymelatonin levels in the early postpartum period.
RESUMEN Objetivos: comparar parámetros del ciclo actividad/descanso en madres lactantes en posparto temprano bajo régimen lumínico de rayos de longitud de onda larga controlado y no controlado. Métodos: estudio cuasiexperimental con madres lactantes y sus bebés, São Paulo, Brasil. Las participantes fueron asignadas a grupos experimental (intervención) y comparación, consistente en exposición en habitación controlada con luz artificial de rayos de longitud de onda larga durante la noche. Se analizaron tiempos de actividad/descanso (horas) y nivel de 6-sulfatoximelatonina a las 24 horas. Resultados: actividad media y tiempos de descanso fueron similares en grupos comparación e intervención. Porcentajes promedio de volumen total de 6-sulfatoximelatonina durante día y noche resultaron similares (p=0,09). A las 24 horas, el grupo intervención presentó porcentaje promedio de volumen total significantemente menor comparado con grupo comparación (p=0,04). Conclusiones: las mujeres expuestas a luz artificial de longitud de onda larga no mostraron diferencias en niveles actividad/descanso y 6-sulfatoximelatonina durante el posparto temprano.
RESUMO Objetivos: comparar os parâmetros do ciclo de atividade/descanso de puérperas lactantes no início do pós-parto sob regime de iluminação com raios de comprimento de onda longo controlado e descontrolado. Métodos: estudo quase-experimental com lactantes e seus bebês em alojamento conjunto, São Paulo, Brasil. Os participantes foram alocados para grupos experimental (intervenção) ou de comparação. A intervenção consistia na exposição em uma sala controlada com iluminação artificial de raios de comprimento de onda longo à noite. Foram analisados os horários de atividade/repouso (horas) e nível de 6-sulfatoximelatonina em 24 horas. Resultados: a atividade média e os tempos de repouso das mulheres nos grupos experimental e comparação foram semelhantes. Os percentuais médios de volume total de 6-sulfatoximelatonina durante o dia e a noite foram semelhantes (p=0,09). Em 24 horas, o grupo experimental apresentou percentual médio significantemente menor de volume total em relação ao grupo comparação (p=0,04). Conclusões: as mulheres que permaneceram no quarto com luz artificial de comprimento de onda longa não apresentaram diferenças nos níveis de atividade/repouso e 6-sulfatoximelatonina no início do período pós-parto.
The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well‐known the ...role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents. The present study investigated the role of melatonin on energy metabolism and in pancreatic function and remodeling during pregnancy and early lactation in rats. The results confirm that the absence of melatonin during pregnancy impairs glucose metabolism. In addition, there is a dysregulation in insulin secretion at various stages of the development of pregnancy and an apparent failure in the glucose‐stimulated insulin secretion during the lactation period, evidencing the role of melatonin on the regulation of insulin secretion. This mechanism seems not to be dependent on the antioxidant effect of melatonin and probably dependent on MT2 receptors. We also observed changes in the mechanisms of death and cell proliferation at the end of pregnancy and beginning of lactation, crucial periods for pancreatic remodeling. The present observations strongly suggest that both functionality and remodeling of the endocrine pancreas are impaired in the absence of melatonin and its adequate replacement, mimicking the physiological increase seen during pregnancy, is able to reverse some of the damage observed. Thus, we conclude that pineal melatonin is important to metabolic adaptation to pregnancy and both the functionality of the beta cells and the remodeling of the pancreas during pregnancy and early lactation, ensuring the return to nonpregnancy conditions.
Introduction: Melatonin is a pineal hormone that has acquired several unique modes of regulating the physiological effects in mammals due to its characteristic phylogenetic history. While melatonin ...exhibits immediate nocturnal effects, it also has next-day prospective effects that take place in the absence of this hormone. Besides that, the daily repetition and the annual variation in the duration of its synthesis determine its circadian and seasonal effects that characterize melatonin as a chronobiotic, a molecule that encodes time to the internal environment. Additionally, it presents transgenerational effects that are important for fetal programming, leading to a balanced energy metabolism in the adult life.
Areas covered: Physiology, pathophysiology and therapeutic value of melatonin in metabolism and metabolic disorders.
Expert opinion: The typical mechanisms of action of melatonin (immediate, prospective, chronobiotic and transgenerational) should be considered to adequately understand its physiological effects on the regulation of metabolism in humans and, as a result, to understand the metabolic pathophysiological consequences caused by its synthesis and/or signaling disturbances. That points to the importance of a broader understanding of melatonin actions, besides the classical endocrinological point of view, that would allow the clinician/research to proper interpret its role in health maintenance.
•Melatonin reduces excitability in N0 neurons of DRG.•DRG of rats express significantly MT1 gene.•Melatonin effects are blocked by the melatonin receptor antagonist luzindole.
Melatonin, a powerful ...antioxidant, participates in the regulation of important physiological and pathological processes. We investigated the actions of melatonin on neuronal excitability of intact dorsal root ganglions (DRG) from rats using intracellular recording techniques in current clamps. Melatonin blocked the generation of action potentials in a concentration-dependent manner. Bath applied melatonin (1.0–1000.0 nM) hyperpolarized the resting membrane potential, and increased the input resistance and rheobase. Melatonin also altered the active electrophysiological properties of the action potential, amplitude and maximum descendant inclination, in a statistically significant way. In order to provide evidence on the mechanism of action of melatonin in the DRG, quantitative PCR (qPCR) was performed. Analyses were performed for melatonin membrane receptors, MT1 and MT2, and it was observed that the DRG expresses MT1 receptors. In addition, we noted that the melatonin-induced effects were blocked in the presence of luzindole, a melatonin receptor antagonist. The minimal effective concentrations of melatonin (10.0 nM) and the blockade of effects caused by luzindole suggest that the effects of melatonin are hormonal, and are induced when it binds to MT1 receptors.
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