Melatonin as a Hormone: New Physiological and Clinical Insights

Endocrine Reviews, Journal Year: 2018, Volume and Issue: 39(6), P. 990 - 1028

Published: Sept. 12, 2018

Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides produced peripheral tissues and acting as an autocrine paracrine signal, melatonin centrally synthetized by neuroendocrine organ, the pineal gland. Independently of considered species, hormone always during night its production secretory episode duration are directly dependent on length night. As tightly linked light/dark cycle, main hormonal systemic integrative action coordinate behavioral physiological adaptations environmental geophysical day season. The circadian signal daily regularity, contrast between concentrations, specially developed ways action. During episode, coordinates adaptive physiology through immediate effects primes responses prospective that will only appear at daytime, when absent. Similarly, annual history central nervous/endocrine system seasons come. Remarkably, maternal programs fetuses' behavior cope with cycle season after birth. These unique turn into biological time-domain–acting molecule. review focuses above considerations, proposes putative classification clinical dysfunctions, discusses general guidelines therapeutic use melatonin.

Language: Английский

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Melatonin receptors: molecular pharmacology and signalling in the context of system bias

British Journal of Pharmacology, Journal Year: 2017, Volume and Issue: 175(16), P. 3263 - 3280

Published: July 14, 2017

Melatonin, N ‐acetyl‐5‐methoxytryptamine, an evolutionally old molecule, is produced by the pineal gland in vertebrates, and it binds with high affinity to melatonin receptors, which are members of GPCR family. Among multiple effects attributed melatonin, we will focus here on those that dependent activation two mammalian MT 1 2 receptors. We briefly summarize latest developments synthetic receptor ligands, including multi‐target‐directed characterization signalling‐biased ligands. discuss signalling pathways activated receptors appear be highly cell‐ tissue‐dependent, emphasizing impact system bias functional outcome. Different proteins have been demonstrated interact thus, postulate part this has its molecular basis differences expression receptor‐associated heterodimerization partners. Finally, at level receptor, genetic variants, discussed show how a modified function can effect risk for common diseases like type diabetes humans. Linked Articles This article themed section Recent Developments Research Melatonin Potential Therapeutic Applications. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

Language: Английский

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Melatonin feedback on clock genes: a theory involving the proteasome

Journal of Pineal Research, Journal Year: 2014, Volume and Issue: 58(1), P. 1 - 11

Published: Nov. 4, 2014

Abstract The expression of ‘clock’ genes occurs in all tissues, but especially the suprachiasmatic nuclei ( SCN ) hypothalamus, groups neurons brain that regulate circadian rhythms. Melatonin is secreted by pineal gland a manner as influenced . There also considerable evidence melatonin, turn, acts on directly influencing mechanisms. most direct route which melatonin could reach would be via cerebrospinal fluid third ventricle. pars tuberalis PT pituitary, another melatonin‐sensitive tissue, this route. major include period genes, Per1 and Per2 , cryptochrome Cry1 Cry2 clock (circadian locomotor output cycles kaput) gene, Bmal1 (aryl hydrocarbon receptor nuclear translocator‐like) gene. Clock heterodimers act E‐box components promoters Per Cry to stimulate transcription. A negative feedback loop between proteins nucleus allows their own cycle ubiquitination deubiquitination controls levels CRY protein degraded proteasome and, hence, amount available for feedback. Thus, it provides post‐translational component mechanism. BMAL 1 stimulates transcription REV ‐ ERB α partially regulated In ‘black widow’ model transcription, proteasomes destroy factors are needed only particular time. proposed herein, interaction required adjust changes environmental photoperiod. particular, we predict inhibition interferes with loops / PER both tend stabilize itself particularly at night when naturally elevated. account effects rhythms associated molecular timing genes. hypothalamus explaining dramatic ‘time day’ effect injections reproductive status seasonal breeders. Finally, predicts inhibitor such bortezomib modify similar melatonin.

Language: Английский

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Exposure to Artificial Light at Night and the Consequences for Flora, Fauna, and Ecosystems

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Nov. 16, 2020

The present review draws together wide-ranging studies performed over the last decades that catalogue effects of artificial-light-at-night (ALAN) upon living species and their environment. We provide an overview tremendous variety light-detection strategies which have evolved in organisms - unicellular, plants animals, covering chloroplasts (plants), plethora ocular extra-ocular organs (animals). describe visual pigments permit photo-detection, paying attention to spectral characteristics, extend from ultraviolet into infrared. discuss how use light information a way crucial for development, growth survival: phototropism, phototaxis, photoperiodism, synchronization circadian clocks. These aspects are treated depth, as perturbation underlies much disruptive ALAN. goes detail on networks organisms, since these fundamental features critical importance regulating interface between environment body. Especially, hormonal synthesis secretion often under circannual control, hence clock will lead imbalance. addresses ubiquitous introduction light-emitting diode technology may exacerbate, or some cases reduce, generalized ever-increasing pollution. Numerous examples given widespread exposure ALAN is perturbing many plant animal behaviour foraging, orientation, migration, seasonal reproduction, colonization more. examine potential problems at level individual populations debate consequences ecosystems. stress, through few examples, synergistic harmful resulting impacts combined with other anthropogenic pressures, impact neuroendocrine loops vertebrates. article concludes by debating changes could be mitigated more reasonable available example restricting illumination essential areas hours, directing lighting avoid wasteful radiation selecting emissions, reduce end discussing society should take account potentially major has natural world repercussions ongoing human health welfare.

Language: Английский

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Mammalian Seasonal Rhythms: Behavior and Neuroendocrine Substrates

Elsevier eBooks, Journal Year: 2016, Volume and Issue: unknown, P. 371 - 398

Published: Nov. 29, 2016

Language: Английский

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Disrupted seasonal biology impacts health, food security and ecosystems

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2015, Volume and Issue: 282(1817), P. 20151453 - 20151453

Published: Oct. 15, 2015

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles physiology, health, morphology, behaviour demography response to environmental cues. Seasonal biology impacts ecosystems agriculture, with consequences for humans biodiversity. Human populations robust rhythms health well-being, birth month can have lasting effects that persist throughout life. This review emphasizes need a better understanding against backdrop its rapidly progressing disruption through climate change, human lifestyles other anthropogenic impact. Climate change modifying which numerous organisms adapted, potential industries relating food security. Disconcertingly, under artificial conditions eternal summer provide most extreme example disconnect from natural seasons, making vulnerable increased morbidity mortality. In this review, we introduce scenarios disruption, highlight key aspects summarize biomedical, anthropological, veterinary, agricultural perspectives recent evidence desynchronization between factors internal rhythms. Because are pervasive across biological systems, they common framework trans-disciplinary research.

Language: Английский

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An integrative view of mammalian seasonal neuroendocrinology

Journal of Neuroendocrinology, Journal Year: 2019, Volume and Issue: 31(5)

Published: May 1, 2019

Abstract Seasonal neuroendocrine cycles that govern annual changes in reproductive activity, energy metabolism and hair growth are almost ubiquitous mammals have evolved at temperate polar latitudes. Changes nocturnal melatonin secretion regulating gene expression the pars tuberalis (PT) of pituitary stalk a critical common feature seasonal mammals. The PT sends signal(s) to distalis regulate prolactin thus moult cycle. also signals retrograde manner via thyroid‐stimulating hormone tanycytes, which line ventral wall third ventricle hypothalamus. Tanycytes show plasticity play pivotal role local thyroid (TH) availability. Within mediobasal hypothalamus, cellular molecular targets TH remain elusive. However, two populations hypothalamic neurones, produce RF‐amide neuropeptides kisspeptin RFRP3 (RF‐amide related peptide 3), plausible relays between gonadotrophin‐releasing hormone‐pituitary‐gonadal axis. By contrast, ways by impinges on systems intake expenditure unknown. Here, we review underpinnings seasonality identify several areas warrant further research.

Language: Английский

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Seasonal control of gonadotropin-inhibitory hormone (GnIH) in birds and mammals

Frontiers in Neuroendocrinology, Journal Year: 2014, Volume and Issue: 37, P. 65 - 75

Published: Dec. 12, 2014

Language: Английский

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Binary Switching of Calendar Cells in the Pituitary Defines the Phase of the Circannual Cycle in Mammals

Current Biology, Journal Year: 2015, Volume and Issue: 25(20), P. 2651 - 2662

Published: Sept. 24, 2015

Highlights•A circannual timer may reside in the pituitary pars tuberalis thyrotroph•This is defined by a digital switching mechanism controlling EYA3 expression•The clockwork drives morphogenic cycle PT and hypothalamus•This involves recapitulation of developmental programSummaryPersistent free-running (approximately year-long) rhythms have evolved animals to regulate hormone cycles, drive metabolic (including hibernation), time annual reproduction. Recent studies photoperiodic input this rhythm, wherein melatonin acts on thyrotroph cells (PT), leading seasonal changes control thyroid metabolism hypothalamus. However, persist constant conditions many species absence changing photoperiod signal, generation cycles. It not known which cells, tissues, pathways generate these remarkable long-term rhythmic processes. We show that individual thyrotrophs can be one two binary states reflecting either long (EYA3+) or short (CHGA+) photoperiod, with relative proportion each state defining phase cycle. also driven leads extensive re-modeling hypothalamus over propose employ recapitulated pathway morphology tissues cells. Our data are consistent hypothesis within encoded switch timing mechanism, neuroendocrine rhythms, dynamic hypothalamic interface. In summary, PT-ventral now appears prime structure involved rhythm generation.Graphical abstract

Language: Английский

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Signaling pathways to and from the hypophysial pars tuberalis, an important center for the control of seasonal rhythms

General and Comparative Endocrinology, Journal Year: 2017, Volume and Issue: 258, P. 236 - 243

Published: May 13, 2017

Language: Английский

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