Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Simonneaux, Valérie; Ribelayga, Christophe

doi:10.1124/pr.55.2.2

Cited by 611 publications

(591 citation statements)

References 1,030 publications

(1,241 reference statements)

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“…These data suggest that HIOMT enzymatic activity determines the level of melatonin synthesis in the above mentioned tissues during aging. In accordance with Simonneaux and Ribelayga, any modification in HIOMT activity could modulate, consequently, the melatonin production phase (Simonneaux and Ribelayga, 2003). In this sense, HIOMT enzyme may be the first key enzyme involved in melatonin synthesis that suffers the consequences of aging.…”

Section: Discussionsupporting

confidence: 53%

Age-related changes in melatonin synthesis in rat extrapineal tissues

Sánchéz-Hidalgo

Lastra

Carrascosa-Salmoral

et al. 2009

Experimental Gerontology

109

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Accepted ManuscriptAge-related changes in melatonin synthesis in rat extrapineal tissues M Sanchez-Hidalgo, C Alarcon de la Lastra, MP Carrascosa-Salmoral, MC Naranjo, A Gomez-Corvera, B Caballero, JM Guerrero PII:S0531-5565 (09) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT AbstractIn the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and antiaging properties.The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3-and 12 monthold rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age.Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.

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Section: Discussionsupporting

confidence: 53%

Age-related changes in melatonin synthesis in rat extrapineal tissues

Sánchéz-Hidalgo

Lastra

Carrascosa-Salmoral

et al. 2009

Experimental Gerontology

109

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“…Melatonin is the biochemical transducer of photoperiodic information to all cells in the body (including SCN neurons), and changes in duration and amplitude of nocturnal secretion serves to signal seasonal variations of day/night cycle length (for review see Simonneaux and Ribelayga, 2003). Autonomic neurons of the PVN communicate time-of-day signal to different organs, and corticotrophin-releasing factor, which is secreted by PVN neurons, indirectly communicates time of day through its circadian rhythmicity entrained by the SCN.…”

Section: The Circadian Systemmentioning

confidence: 99%

Does the circadian system regulate lactation?

Plaut

Casey

2012

Animal

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Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/ clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.Keywords: mammary, lactation, circadian rhythm, photoperiod, metabolism ImplicationsThe circadian system coordinates internal physiological processes in mammals and synchronizes these processes to the animal's environment. We review the literature and discuss recent findings from our laboratory and others that suggest the circadian system regulates lactation, including coordinating changes in the dam's physiology needed to initiate and maintain lactation and mediating the photoperiod effect on milk production. Identification of environmental and physiological inputs that affect genes that control circadian rhythms will enable development of approaches to alter gene expression to maximize production efficiency in farm animals. IntroductionNearly all physiological and behavioral functions of animals are rhythmic including secretion patterns of hormones, sleep-wake cycle, metabolism and core body temperature.A circadian rhythm is a roughly 24-h cycle in the biochemical, physiological or behaviora...

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“…This is mainly derived from the superior cervical ganglion, which receives signals from the retina via the suprachiasmatic and paraventricular nuclei in the hypothalamus. In addition, a plethora of inputs that employ the same pathway, as well as circulating transmitters and hormones, are integrated and affect the function of the pinealocytes and the release of melatonin [14].…”

Section: Pineal Secretion Of Melatoninmentioning

confidence: 99%

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

et al. 2009

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Melatonin is a circulating hormone that is primarily released from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms; its levels are high during the night and low during the day. Interestingly, insulin levels also exhibit a nocturnal drop, which has previously been suggested to be controlled, at least in part, by melatonin. This regulation can be explained by the proposed inhibitory action of melatonin on insulin release. Indeed, both melatonin receptor 1A (MTNR1A) and MTNR1B are expressed in pancreatic islets. The role of melatonin in the regulation of glucose homeostasis has been highlighted by three independent publications based on genome-wide association studies of traits connected with type 2 diabetes, such as elevated fasting glucose, and, subsequently, of the disease itself. The studies demonstrate a link between variations in the MTNR1B gene, hyperglycaemia, impaired early phase insulin secretion and beta cell function. The risk genotype predicts the future development of type 2 diabetes. Carriers of the risk genotype exhibit increased expression of MTNR1B in islets. This suggests that these individuals may be more sensitive to the actions of melatonin, leading to impaired insulin secretion. Blocking the inhibition of insulin secretion by melatonin may be a novel therapeutic avenue for type 2 diabetes.

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Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Cited by 611 publications

References 1,030 publications

Age-related changes in melatonin synthesis in rat extrapineal tissues

Age-related changes in melatonin synthesis in rat extrapineal tissues

Does the circadian system regulate lactation?

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

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