Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circadian genes are expressed in virtually all cells and tissues, and circadian rhythms influence many bodily processes, including reproductive physiology. The expression of hMTNR1B is suppressed during pregnancy until late in term (much like the oxytocin receptor), at which time it is up-regulated to allow for the nocturnal melatonin/oxytocin synergy, which promotes strong nocturnal contractions. Little is currently known about the regulation of hMNTR1b, nor about its functional significance in the myometrium. We, therefore, aimed to elucidate some of the transcription factors that regulate hMNTR1b gene expression in the human myometrium and to determine if hMNTR1b is under circadian control. In this study, we used immortalized and primary myometrial cells that were assessed for circadian gene expression rhythms using real-time bioluminometry and quantitative PCR. Chromatin immunoprecipitation examined the binding of the clock gene product brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) to the promoter of the hMTNR1B gene. Overexpression studies tested the role of circadian locomotor output cycles kaput (CLOCK) and its partner BMAL1 in regulating hMTNR1B expression. We confirmed circadian clock gene expression in both immortalized human myometrial cells and primary myometrial cell cultures. We further showed that the hBMAL1 protein binds to an E-box motif in the proximal promoter of the hMTNR1B gene. Overexpression studies demonstrated that the BMAL1/CLOCK complex activates expression of hMTNR1B leading to a circadian rhythm in phase with the E-box driven clock gene hPER2 (Period 2). These results indicate, for the first time, the presence of a functional circadian clock in the human myometrium with the hMTNR1B gene as a clock controlled target. Further investigations could open new vistas for understanding the regulation of uterine contractions and the timing of human labor.
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PMID:Circadian clock regulation of melatonin MTNR1B receptor expression in human myometrial smooth muscle cells. 2593 54

There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin's effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.
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PMID:The Role of Prenatal Melatonin in the Regulation of Childhood Obesity. 3226 May 29