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Testosterone signaling in spermatogenesis, male fertility and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Arijit Chakraborty, Vertika Singh, Kiran Singh, Rajender Singh
Melatonin is an indoleamine, which is a major secretory product of the pineal gland. It regulates the circadian cycle and acts as a cytokine, neuromodulator and biological response modifier. This hormone functions as a regulator of the reproductive physiology in response to environmental light in seasonally dependent mammals. It displays both hydrophilic and lipophilic properties and can enter testicular cells by crossing the blood-testis barrier. Multiple studies have demonstrated the localization of melatonin receptors on the reproductive system with primary target sites on the testis, epididymis, vas deferens, prostate and ovary. Melatonin is also suggested to regulate the timing for the release of hormones in the female reproductive system. It can act through several receptors such as melatonin receptor 1 (MT1), melatonin receptor 2 (MT2) and retinoid acid receptor–related orphan receptor A (RORα) (28). MT1 and MT2 interact with G-protein to regulate testosterone synthesis by modulating cAMP signal transduction (29). Research suggests that RORα directly activates the aromatase to accelerate the conversion of androgens into estrogens (30).
Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder
Published in Expert Review of Clinical Pharmacology, 2022
In humans, melatonin is a full agonist of the G-protein coupled receptors (GPCRs), melatonin receptor 1 (MT1, melatonin binding affinity in the picomolar range), and melatonin receptor 2 (MT2 melatonin binding affinity in the nanomolar range) [84]. MT1 and MT2 melatonin receptor mRNA were detected in various areas of the human brain including retina cerebral cortex hypothalamus (including the SCN) midbrain and cerebellum [84]. Melatonin also acts as a high-capacity free radical scavenger within mitochondria [85]. Functional magnetic resonance imaging (fMRI) studies indicated that ingestion 2 mg melatonin elicits sleep-like effects on functional activities in the human brain occipital cortex (specifically the precuneus), hippocampus, and the auditory cortex [86]. These are compatible with the presence of melatonin receptors in these areas and the pharmacodynamic effects of orally ingested melatonin on brain function.
Circadian characteristics of the rest-activity rhythm, executive function, and glucose fluctuations in young adults with type 1 diabetes
Published in Chronobiology International, 2021
Stephanie Griggs, Kingman P. Strohl, Margaret Grey, Eric Barbato, Seunghee Margevicius, Ronald L. Hickman
Monitoring over a longer period of time is needed to determine the extent to which rest-activity rhythms predict glycemia over times longer than a fortnight, including unanticipated events or activities and capture other important diabetes outcomes (e.g., emotional distress and executive function) and to facilitate the understanding of temporal ordering. Melatonin is an important determinant of circadian rhythmicity, yet synthesis of melatonin was found to be impaired in rat models of diabetes both in vivo and in vitro and adults with T1D during periods of high blood glucose concentrations in a recent study (Amaral et al. 2014). There is growing evidence of a relationship between melatonin, diabetes, and metabolic syndrome whereby variation in gene encoding the melatonin receptor 1b (MTNR1B) appears to be involved in impaired insulin secretion and ineffective glucose metabolism in humans (Bouatia-Naji et al. 2009; Prokopenko et al. 2009). Additionally, melatonin supplementation reduced both hyperglycemia and hyperlipidemia and improved the antioxidant status in rats with diabetes (Montilla et al. 1998; Nishida et al. 2002). The role of variation in melatonin rhythm with glucose fluctuations and exogenous lighting and other zeitgebers as well as the rest-activity rhythm should be examined in this population.
The pharmacotherapeutic management of postoperative delirium: an expert update
Published in Expert Opinion on Pharmacotherapy, 2020
Another example of a personalized medicine approach is in the area of sleep where research has indicated that a single nucleotide polymorphism in the melatonin receptor 1B gene in homozygotes can lead to altered melatonin signaling and sleep pathology including aberrant longer duration of melatonin levels and delayed decrease in melatonin after light exposure. In a recent study of patients undergoing cardiac surgery, those with the homozygote genotype showed an increased risk for development of POD compared to those without this profile. Therefore, the studies that have been previously done with melatonin as a way to prevent delirium may have actually delivered skewed results because the patients were arbitrarily given melatonin without benefit of genotyping and thus a tailored approach could lead to a more informative treatment plan for an individual [126].