Publication Cover
Archives of Physiology and Biochemistry
The Journal of Metabolic Diseases
Volume 128, 2022 - Issue 5
931
Views
25
CrossRef citations to date
0
Altmetric
Review Article

Physiological and pharmacological perspectives of melatonin

Pages 1346-1367 | Received 06 Mar 2020, Accepted 13 May 2020, Published online: 10 Jun 2020

References

  • Abadir, P.M., et al., 2006. Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension (Dallas, Tex.: 1979), 48 (2), 316–322.
  • Acuña-Castroviejo, D., et al., 2014. Extrapineal melatonin: Sources, regulation, and potential functions. Cellular and molecular life sciences: Cmls, 71 (16), 2997–3025. doi:10.1007/s00018-014-1579-2
  • Adamczyk-Sowa, M., et al., 2014. Influence of melatonin supplementation on serum antioxidative properties and impact of the quality of life in multiple sclerosis patients. Journal of physiology and pharmacology : an official journal of the Polish physiological society, 65 (4), 543–550.
  • Afeche, S. C., et al., 2008. Melatonin and the pineal gland. In: Romano E, De Luca S, eds. New research on neurosecretory systems. New York: Nova Biomedical Books, p. 151–177.
  • Afroz, H., et al., 2015. Microscopic study on the shape of pineal calcification of Bangladeshi cadavers. Journal of Dhaka Medical College, 22 (2), 151–155.
  • Agez, L., et al., 2007. Melatonin affects nuclear orphan receptors mRNA in the rat suprachiasmatic nuclei. Neuroscience, 144 (2), 522–530.
  • Aleandri, V., Spina, V., and Morini, A., 1996. The pineal gland and reproduction. Human reproduction update, 2 (3), 225–235.
  • Alicelebić, S., et al., 2006. The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland. Bosnian journal of basic medical sciences, 6 (4), 18–21.
  • Alkozi, H.A., et al., 2018. Docking studies for melatonin receptors. Expert opinion on drug discovery, 13 (3), 241–248.
  • American Academy of Sleep Medicine 2014. International classification of sleep disorders. 3rd ed. Darien (IL): American Academy of Sleep Medicine.
  • Amihăesei, I.C., and Mungiu, O.C., 2012. Main neuroendocrine features and therapy in primary sleep troubles. Revista medico-chirurgicala a societatii de medici si naturalisti din iasi, 116 (3), 862–866.
  • Anisimov, V.N., et al., 2000. Melatonin and colon carcinogenesis III. Effects of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethylhydrazine in rats. Experimental and toxicologic pathology., 52 (1), 71–76.
  • Arendt, J., and Skene, D.J., 2005. Melatonin as a chronobiotic. Sleep medicine reviews, 9 (1), 25–39.
  • Arendt, J., 2019. Melatonin: countering chaotic time cues. Frontiers in endocrinology, 10, 391.
  • Bahna, S.G., and Niles, L.P., 2018. Epigenetic regulation of melatonin receptors in neuropsychiatric disorders. British journal of pharmacology, 175 (16), 3209–3219.
  • Bajova, H., Nelson, T.E., and Gruol, D.L., 2008. Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-kappaB in hippocampal neuronal cell culture. Journal of neuroimmunology, 195 (1-2), 36–46.
  • Bartlett, D.J., Biggs, S.N., and Armstrong, S.M., 2013. Circadian rhythm disorders among adolescents: assessment and treatment options. The medical journal of Australia, 199 (8), S16–S20.
  • Bartness, T.J., Demas, G.E., and Song, C.K., 2002. Seasonal changes in adiposity: the roles of the photoperiod, melatonin and other hormones, and sympathetic nervous system. Experimental biology and medicine (Maywood, N.J.), 227 (6), 363–376.
  • Benaim, G., and Villalobo, A., 2002. Phosphorylation of calmodulin. Functional implications. European journal of biochemistry, 269 (15), 3619–3631.
  • Benitez-King, G., 2006. Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. Journal of pineal research, 40 (1), 1–9.
  • Benna, C., et al., 2017. Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis. Oncotarget, 8 (14), 23978–23995.
  • Berga, S., et al., 1988. Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. The journal of clinical endocrinology and metabolism, 66 (1), 242–244.
  • Bersani, G., et al., 1999. Computed tomography study of pineal calcification in schizophrenia. European psychiatry: The journal of the Association of European Psychiatrists, 14 (3), 163–166.
  • Bhat, S.A., et al., 2017. Synopsis on Managment strategies for neurodegenerative disorders: challenges from bench to bedside in successful drug discovery and development. Current topics in medicinal chemistry, 17 (12), 1371–1378.
  • Biran, V., et al., 2014. Is melatonin ready to be used in preterm infants as a neuroprotectant? Developmental medicine and child neurology, 56 (8), 717–723.
  • Bizzarri, M., et al., 2013. Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review. Expert opinion on therapeutic targets, 17 (12), 1483–1496.
  • Bojkowski, C.J., et al., 1987. Suppression of nocturnal plasma melatonin and 6-sulphatoxymelatonin by bright and dim light in man. Hormone and metabolic research = hormon- und stoffwechselforschung = hormones et metabolisme, 19 (9), 437–440.
  • Bondy, S., and Campbell, A., 2018. Mechanisms underlying tumor suppressive properties of melatonin. International journal of molecular sciences, 19 (8), 2205.
  • Bonnefond, A., et al.,; The Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC). 2012. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nature genetics, 44 (3), 297–301..
  • Bouatia-Naji, N., et al., 2009. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nature genetics, 41 (1), 89–94.
  • Boutin, J.A., et al., 2008. Studies of the melatonin binding site location onto quinone reductase 2 by directed mutagenesis. Archives of biochemistry and biophysics, 477 (1), 12–19.
  • Brainard, G.C., et al., 2001. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. The journal of neuroscience: the official journal of the society for neuroscience, 21 (16), 6405–6412.
  • Brown, R., et al., 1985. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. The American journal of psychiatry, 142 (7), 811–816.,
  • Brydon, L., et al., 2001. Functional expression of mt2 (mel1b) melatonin receptors in human paz6 adipocytes. Endocrinology, 142 (10), 4264–4271.
  • Brzezinski, A., 1997. Melatonin in humans. The New England journal of medicine, 336 (3), 186–195.
  • Bubenik, G.A., 2002. Gastrointestinal melatonin: localization, function, and clinical relevance. Digestive diseases and sciences, 47 (10), 2336–2348.
  • Buijs, R.M., et al., 2003. The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. The journal of endocrinology, 177 (1), 17–26.
  • Bumb, J.M., et al., 2014. Pineal gland volume in primary insomnia and healthy controls: A magnetic resonance imaging study. Journal of sleep research, 23 (3), 276–282.
  • Burgess, H.J., Sharkey, K.M., and Eastman, C.I., 2002. Bright light, dark and melatonin can promote circadian adaptation in night shift workers. Sleep medicine reviews, 6 (5), 407–420.
  • Cardinali, D.P., et al., 1997. Melatonin site and mechanism of action: Single or multiple?. Journal of pineal research, 23 (1), 32–39.
  • Caroleo, M.C., et al., 1992. Melatonin as immunomodulatory in immunodeficient mice. Immunopharmacology, 23 (2), 81–89.
  • Carrillo-Vico, A., et al., 2003. Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its MT1 membrane receptor. FASEB journal: official publication of the federation of American societies for experimental biology, 17 (6), 755–757.
  • Carrillo-Vico, A., et al., 2005. A review of the multiple actions of melatonin on the immune system. Endocrine, 27 (2), 189–200.
  • Carrillo-Vico, A., et al., 2013. Melatonin: buffering the immune system. International journal of Molecular sciences, 14 (4), 8638–8683.
  • Castel, M., and Morris, J.F., 2000. Morphological heterogeneity of the GABAergic network in the suprachiasmatic nucleus, the brain’s circadian pacemaker. Journal of anatomy, 196 (1), 1–13.
  • Cecon, E., et al., 2010. Daily variation of constitutively activated nuclear factor kappa B (NFKB) in rat pineal gland. Chronobiology international, 27 (1), 52–67.
  • Chakraborty, J., et al., 2014. Melatonin protects against behavioural dysfunctions and dendritic spine damage in 3-nitropropionic acid-induced rat model of Huntington's disease. Behavioural brain research, 264, 91–104.
  • Chin, D., and Means, A.R., 2000. Calmodulin: a prototypical calcium sensor. Trends in cell biology, 10 (8), 322–328.
  • Chuang, J.I., Chen, S.S., and Lin, M.T., 1993. Melatonin decreases brain serotonin release, arterial pressure and heart rate in rats. Pharmacology, 47 (2), 91–97.
  • Chuang, J.I., et al., 2016. Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment. Journal of pineal research, 61 (2), 230–240.
  • Claustrat, B., et al., 1984. A chronobiological study of melatonin and cortisol secretion in depressed subjects: Plasma melatonin, a biochemical marker in major depression. Biological Psychiatry, 19, 1215–1228.
  • Comai, S., Ochoa-Sanchez, R., and Gobbi, G., 2013. Sleep-wake characterization of double MT1/MT2 receptor knockout mice and comparison with MT1 and MT2 receptor knockout mice . Behavioural brain research, 243, 231–238.
  • Cortese, S., et al., 2013. Assessment and management of sleep problems in youths with attention-deficit/hyperactivity disorder. Journal of the American academy of child and adolescent psychiatry, 52 (8), 784–796.
  • Cortese, S., et al., 2006. ADHD and insomnia. Journal of the American academy of child and adolescent psychiatry, 45 (4), 384–385.
  • Costa, G., Haus, E., and Stevens, R., 2010. Shift work and cancer - considerations on rationale, mechanisms, and epidemiology. Scandinavian journal of work, environment and health, 36 (2), 163–179.
  • Dax, E.M., and Sugden, D., 1988. Age-associated changes in pineal adrenergic receptors and melatonin synthesizing enzymes in the Wistar rat. Journal of neurochemistry, 50 (2), 468–472.
  • de Borsetti, N.H., et al., 2011. Light and melatonin schedule neuronal differentiation in the habenular nuclei. Developmental biology, 358 (1), 251–261.
  • de Paula, R.M., et al., 2008. A connection between mapk pathways and circadian clocks. Cell cycle (Georgetown, Tex.).), 7 (17), 2630–2634.
  • Del Río, B., et al., 2004. Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. The journal of biological chemistry, 279 (37), 38294–38302.
  • Den Boer, J.A., Bosker, F.J., and Meesters, Y., 2006. Clinical efficacy of agomelatine in depression: the evidence. International clinical psychopharmacology, 21 (1), S21–S24.
  • Deng, Y.Q., et al., 2005. Effects of melatonin on wortmannin-induced tau hyperphosphorylation. Acta pharmacologica sinica, 26 (5), 519–526.
  • Ding, M., et al., 2018. Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin. Journal of pineal research, 64 (1), e12447.
  • do Amaral, G.F., and Cipolla-Neto, J., 2018. A brief review about melatonin, a pineal hormone. Archives of endocrinology and metabolism, 62 (4), 472–479.
  • Do, M.T., and Yau, K.W., 2010. Intrinsically photosensitive retinal ganglion cells. Physiological reviews, 90 (4), 1547–1581.
  • Domínguez-Alonso, A., et al., 2015. Melatonin stimulates dendrite formation and complexity in the hilar zone of the rat hippocampus: participation of the Ca++/calmodulin complex. International journal of molecular sciences, 16 (1), 1907–1927. doi:10.3390/ijms16011907
  • Douglas-Hall, P., and Whicher, E.V., 2015. As required’ medication regimens for seriously mentally ill people ill people in hospital. Cochrane database of systematic review, 12, CD003441.
  • Doyle, A.J., and Anderson, G.D., 2006. Physiologic calcification of the pineal gland in children on computed tomography: prevalence, observer reliability and association with choroid plexus calcification. Academic radiology, 13 (7), 822–826.
  • Drexler, J., 1963. The calcified pineal body and mammary carcinoma. Cancer, 16 (12), 1616–1617.
  • Dubocovich, M.L., et al., 2010. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacological reviews, 62 (3), 343–380.
  • Ebisawa, T., et al., 1994. Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores. Proceedings of the national academy of sciences of the United States of America, 91 (13), 6133–6137.
  • Ekmekcioglu, C., 2006. Melatonin receptors in humans: biological role and clinical relevance. Biomedicine and pharmacotherapy = biomedecine and pharmacotherapie, 60 (3), 97–108.
  • Ekstrom, P., and Meissl, H., 2003. Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors. Philosophical Transactions of the Royal Society of London. Series B, biological sciences, 358 (1438), 1679–1700.
  • Erdos, E.G., Tan, F., and Skidgel, R.A., 2010. Angiotensin I-converting enzyme inhibitors are allosteric enhancers of kinin B1 and B2 receptor function. Hypertension (Dallas, Tex.: 1979)), 55 (2), 214–220.
  • Erlich, S.S., and Apuzzo, M.L., 1985. The pineal gland: anatomy, physiology, and clinical significance. Journal of neurosurgery, 63 (3), 321–341.
  • Farhud, D., and Aryan, Z., 2018. Circadian rhythm, lifestyle and health: a narrative review. Iranian journal of public health, 47 (8), 1068–1076.
  • Farhud, D., and Tahavorgar, A., 2012. Melatonin hormone, metabolism and its clinical effects. Iranian journal of endocrinology and metabolism, 2, 211–223.
  • Ferreira, Z.S., et al., 2005. Corticosterone modulates noradrenaline-induced melatonin synthesis through inhibition of nuclear factor kappa B. Journal of pineal research, 38 (3), 182–188.
  • Filipski, E., et al., 2004. Effects of chronic jet lag on tumor progression in mice. Cancer research, 64 (21), 7879–7885.
  • Fisher, S.P., and Sugden, D., 2010. Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle. Sleep, 33 (6), 833–840. doi:10.1093/sleep/33.6.833
  • Fjelldal, P.G., et al., 2004. Pinealectomy induces malformation of the spine and reduces the mechanical strength of the vertebrae in Atlantic salmon, Salmo salar. Journal of pineal research, 36 (2), 132–139.
  • Friedland, R.P., Luxenberg, J.S., and Koss, E., 1990. A quantitative study of intracranial calcification in dementia of the Alzheimer type. International psychogeriatrics, 2 (1), 36–43.
  • Fu, L., and Lee, C.C., 2003. The circadian clock: pacemaker and tumour suppressor. Nature reviews cancer, 3 (5), 350–361.
  • Gallego, M., et al., 2006. An opposite role for tau in circadian rhythms revealed by mathematical modeling. Proceedings of the national academy of sciences of the United States of America, 103 (28), 10618–10623.
  • Geoffroy, P.A., et al.; membres du consensus Mélatonine SFRMS. 2019. The use of melatonin in adult psychiatric disorders: Expert recommendations by the French institute of medical research on sleep (SFRMS). L'Encephale, 45 (5), 413–423. doi:10.1016/j.encep.2019.04.068
  • Gheban, B.A., Rosca, I.A., and Crisan, M., 2019. The morphological and functional characteristics of the pineal gland. Medicine and pharmacy reports, 92 (3), 226–234.
  • Gilad, E., et al., 1999. Melatonin receptors in PC3 human prostate tumor cells. Journal of pineal research, 26 (4), 211–220.
  • Golan, J., et al., 2002. Morphometric parameters of the human pineal gland in relation to age, body weight and height. Folia morphologica, 61 (2), 111–113.
  • Goldman, S.E., et al., 2014. Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep. Journal of autism and developmental disorders, 44 (10), 2525–2535.
  • Gomez-Gonzalez, B., et al., 2012. Role of sleep in the regulation of the immune system and the pituitary hormones. Annals of the New York academy of sciences, 1261, 97–106.
  • Gonzalez-Gonzalez, A., Mediavilla, M.D., and Sanchez-Barcelo, E.J., 2018. Melatonin: a molecule for reducing breast cancer risk. Molecules, 23, E336.
  • Gooley, J.J., et al., 2001. Melanopsin in cells of origin of the retinohypothalamic tract. Nature neuroscience, 4 (12), 1165
  • Grosshans, M., et al., 2016. The association of pineal gland volume and body mass in obese and normal weight individuals: A pilot study. Psychiatria danubina, 28 (3), 220–224.
  • Guermonprez, L., Ducrocq, C., and Gaudry-Talarmain, Y.M., 2001. Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants. Molecular pharmacology, 60 (4), 838–846.
  • Gwinner, E., 1986. Circannual rhythms. Endogenous annual clocks in the organization of seasonal processes. Berlin: Springer,
  • Hablitz, L.M., et al., 2015. GIRK channels mediate the nonphotic effects of exogenous melatonin. Journal of neuroscience, 35 (45), 14957–14965. doi:10.1523/JNEUROSCI.1597-15.2015
  • Hannibal, J., et al., 2004. Melanopsin is expressed in PACAP-containing retinal ganglion cells of the human retinohypothalamic tract. Investigative ophthalmology and visual science, 45 (11), 4202–4209.
  • Hansen, J., 2017. Night shift work and risk of breast cancer. Current environmental health reports, 4 (3), 325–339.
  • Hansen, M.V., et al., 2014. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast cancer research and treatment, 145 (3), 683–695.
  • Hansen, M.V., et al., 2014. The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology, 24 (11), 1719–1728.
  • Hastings, M.H., et al., 1985. Annual reproductive rhythms in mammals: Mechanisms of light synchronization. Annals of the New York academy of sciences, 453, 182–204.
  • Hattar, S., et al., 2003. Melanopsin and rod-cone photoreceptive systems account for all accessory major visual functions in mice. Nature, 424 (6944), 76–81.
  • He, H., Dong, W., and Huang, F., 2010. Anti-amyloidogenic and anti-apoptotic role of melatonin in Alzheimer disease. Current neuropharmacology, 8 (3), 211–217.
  • Henden, T., et al., 1992. Age-associated reduction in pineal beta-adrenergic receptor density is prevented by life-long food restriction in rats. Biological signals, 1 (1), 34–39.
  • Herxheimer, A., and Petrie, K.J., 2002. Melatonin for preventing and treating jet lag. Cochrane database of systematic review, 2, CD001520. doi:10.1002/14651858.CD001520
  • Hill, S.M., et al., 2015. Melatonin: an inhibitor of breast cancer. Endocrine-related cancer, 22 (3), R183–204.
  • Hill, S.M., et al., 1999. Melatonin synergizes with retinoic acid in the prevention and regression of breast cancer. Advances in experimental medicine and biology, 460, 345–362.
  • Holvoet, E., and Gabriels, L., 2013. Disturbed sleep in children with ADHD: is there a place for melatonin as a treatment option? Tijdschr psychiatr, 55, 349–357.
  • Hu, D.N., and Roberts, J.E., 1997. Melatonin inhibits growth of cultured human uveal melanoma cells. Melanoma research, 7 (1), 27–31.
  • Huang, S.H., Cao, X.J., and Wei, W., 2008. Melatonin decreases TLR3-mediated inflammatory factor expression via inhibition of NF-kappa B activation in respiratory syncytial virus-infected RAW264.7 macrophages. Journal of pineal research, 45 (1), 93–100.
  • Ibañez Rodriguez, M.P., Noctor, S.C., and Muñoz, E.M., 2016. Cellular basis of pineal gland development: Emerging role of microglia as phenotype regulator. PLoS One, 11 (11), e0167063
  • Ivanov, I.I., et al., 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell, 126 (6), 1121–1133.
  • Iwasaki, S., et al., 2005. Melatonin as a local regulator of human placental function. Journal of pineal research, 39 (3), 261–265.
  • Jack, C.R., Jr., et al., 2010. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The lancet. neurology, 9 (1), 119–128.
  • Jetten, A.M., 2009. Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. Nuclear receptor signaling, 7, e003
  • Jockers, R., et al., 2016. Update on melatonin receptors: IUPHAR Review 20. British journal of. pharmacology, 173 (18), 2702–2725.
  • Jockers, R., et al., 2008. Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new? British journal of pharmacology, 154 (6), 1182–1195.
  • Joseph, D., et al., 2015. Getting rhythm: how do babies do it? Archives of disease in childhood. fetal and neonatal edition, 100 (1), F50–F54.
  • Jung, K.H., et al., 2009. Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappaB during prevention of oxidative liver injury in a dimethylnitrosamine model. Journal of pineal research, 47 (2), 173–183.
  • Kalsbeek, A., Teclemariam-Mesbah, R., and Pévet, P., 1993. Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus). The journal of comparative neurology, 332 (3), 293–314.
  • Kalsbeek, A., et al., 1996. A diurnal rhythm of stimulatory input to the hypothalamopituitary-adrenal system as revealed by timed intrahypothalamic administration of the vasopressin V1 antagonist. The journal of neuroscience : the official journal of the society for neuroscience, 16 (17), 5555–5565.
  • Kaminski, R.S.R., et al., 2015. Melatonin prevents hyperglycemia in a model of sleep apnea. Archives of endocrinology and metabolism, 59 (1), 66–70.
  • Kandalepas, P.C., Mitchell, J.W., and Gillette, M.U., 2016. Melatonin signal transduction pathways require e-box-mediated transcription of Per1 and Per2 to reset the SCN clock at dusk. Plos one, 11 (6), e0157824.
  • Karolczak, M., Korf, H.W., and Stehle, J.H., 2005. The rhythm and blues of gene expression in the rodent pineal gland. Endocrine, 27 (2), 89–100.
  • Kauppila, A., et al., 1987. Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity. The journal of. clinical endocrinology and metabolism, 65 (5), 823–828.
  • Kennaway, D.J., 2000. Melatonin and development: physiology and pharmacology. Seminars in perinatology, 24 (4), 258–266.
  • Kennedy, S.H., et al., 1996. Nocturnal melatonin and 24-h 6-sulphatoxymelatonin levels in various phases of bipolar affective disorder. Psychiatry research, 63 (2-3), 219–222.
  • Kiefer, T., et al., 2002. Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells. Breast cancer research and treatment, 71 (1), 37–45.
  • Kilic, E., et al., 2008. Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice. Journal of pineal research, 45 (2), 142–148.
  • Klein, D.C., Moore, R.Y., Reppert S.M., eds. 1991. Suprachiasmatic nucleus: The mind’s clock.New York: Oxford University Press. pp, 467.
  • Klein, D.C., 2007. Arylalkylamine N-acetyltransferase: "the Timezyme". The journal of biological chemistry, 282 (7), 4233–4237.
  • Kondoh, T., et al., 2002. Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats. Life sciences, 72 (4-5), 583–590.
  • Kong, X., et al., 2008. Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cellular and molecular neurobiology, 28 (4), 569–579.
  • Konturek, S.J., et al., 2007. Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (GIT). Journal of physiology and pharmacology: an official journal of the polish physiological society, 58 (3), 381–405.
  • Koshy, S., and Vettivel, S.K., 2001. Varying appearances of calcification in human pineal gland: a light microscopic study. Journla of the anatamical society of India, 50 (1), 17–18.
  • Koyama, H., et al., 2002. Melatonin at pharmacologic doses increases bone mass by suppressing resorption throught downregulation of the RANKLmediated osteoclast formation and activation. Journal of bone and mineral research, 17 (7), 1219–1229.
  • Krakowski, G., and Cieciura, L., 1985. Ultrastructural studies on the pinealocyte mitochondria during the daytime and at night. Journal of pineal research, 2 (4), 315–324.
  • Kunz, D., et al., 1998. On pineal calcification and its relation to subjective sleep perception: a hypothesis-driven pilot study. Psychiatry research, 82 (3), 187–191.
  • Kus, I., et al., 2004. Light and electron microscopic examination of pineal gland in rats exposed to constant light and constant darkness. Neuro endocrinology letters, 25 (1-2), 102–108.
  • la Fleur, S.E., et al., 2001. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations. Journal of neuroendocrinology, 13 (12), 1025–1032.
  • Lahiri, D.K., et al., 2004. Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortex. Journal of pineal research, 36 (4), 224–231.
  • Lahiri, D.K., 1999. Melatonin affects the metabolism of the beta-amyloid precursor protein in different cell types. Journal of pineal research, 26 (3), 137–146.
  • Lai, M.C., Lombardo, M.V., and Baron-Cohen, S., 2014. Autism. Lancet (London, England), 383 (9920), 896–910.
  • Lambert HH. 1969. Response of the rat ovary to continuous light: effects of light frequency, intensity and duration of exposure. Doctoral Dissertations. 912. https://scholars.unh.edu/dissertation/912
  • Lane, J.M., et al., 2016. Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes, 65 (6), 1741–1751.
  • Laudon, M., and Frydman-Marom, A., 2014. Therapeutic effects of melatonin receptor agonists on sleep and comorbid disorders. International journal of molecular sciences, 15 (9), 15924–15950.
  • Lavie, P., 1997. Melatonin: Role in gating nocturnal rise in sleep propensity. Journal of biological rhythms, 12 (6), 657–665.
  • Lee, E.J., et al., 2005. Melatonin attenuates gray and white matter damage in a mouse model of transient focal cerebral ischemia. Journal of pineal research, 38 (1), 42–52.
  • Lee, M.Y., et al., 2007. Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. Journal of pineal research, 42 (3), 297–309.
  • Leger, D., Laudon, M., and Zisapel, N., 2004. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. The American journal of medicine, 116 (2), 91–95.
  • Leja-Szpak, A., et al., 2010. Melatonin induces pro-apoptotic signaling pathway in human pancreatic carcinoma cells (PANC-1)). Journal of pineal research, 49 (3), 248–255.
  • Lerner, A.B., et al., 1958. Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocyteS1. Journal of the American Chemical Society, 80 (10), 2587–2587.
  • Lewy, A.J., et al., 2006. The circadian basis of winter depression. Proceedings of the national academy of sciences of the United States of America, 103 (19), 7414–7419.
  • Lewy, A.J., et al., 1980. Light suppresses melatonin secretion in humans. Science (New York, N.Y.).), 210 (4475), 1267–1269.
  • Lewy, A.J., 2003. Clinical applications of melatonin in circadian disorders. Dialogues in clinical neuroscience, 5 (4), 399–413.
  • Li, D.Y., et al., 2013. Melatonin receptor genes in vertebrates. International journal of molecular sciences, 14 (6), 11208–11223.
  • Liu, C., et al., 1997. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron, 19 (1), 91–102.
  • Liu, J., et al., 2016. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annual review of pharmacology and toxicology, 56, 361–383.
  • Liu, L., Ying Xu, Y., and Reiter, R.J., 2013. Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63. Bone, 55 (2), 432–438.
  • López-González, A., et al., 2015. Melatonin treatment improves primary progressive multiple sclerosis: A case report. Journal of pineal research, 58 (2), 173–177.
  • Lotufo, C.M., Lopes, C., et al., 2001. Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. European journal of pharmacology, 430 (2-3), 351–357.
  • Lotufo, C.M., et al., 2006. Melatonin effect on endothelial cells reduces vascular permeability increase induced by leukotriene B4. European journal of pharmacology, 534 (1-3), 258–263.
  • Luboshitzky, R., et al., 2000. Melatonin hypersecretion in male patients with adult-onset idiopathic hypogonadotropic hypogonadism. Experimental and Clinical Endocrinology & Diabetes : official Journal, German Society of Endocrinology [and] German Diabetes Association, 108 (2), 142–145.
  • Lyssenko, V., et al., 2009. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nature genetics, 41 (1), 82–88.
  • Macchi, M.M., and Bruce, J.N., 2004. Human pineal physiology and functional significance of melatonin. Frontiers in neuroendocrinology, 25 (3-4), 177–195.
  • Macleod, M.R., et al., 2005. Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke. Journal of pineal research, 38 (1), 35–41.
  • Marcola, M., et al., 2013. Endothelial cell adhesiveness is a function of environmental lighting and melatonin level. Journal of pineal research, 54 (2), 162–169.
  • Markus, R.P., Cecon, E., and Pires-Lapa, M.A., 2013. Immune-pineal axis: nuclear factor κB (NF-kB) mediates the shift in the melatonin source from pinealocytes to immune competent cells. International journal of molecular sciences, 14 (6), 10979–10997.
  • Markus, R.P., et al., 2018. Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. British journal of pharmacology, 175 (16), 3239–3250.
  • Markus, R.P., et al., 2007. The immune-pineal axis: a shuttle between endocrine and paracrine melatonin sources. Neuroimmunomodulation, 14 (3-4), 126–133.
  • Markus, R.P., and Ferreira, Z.S., 2011. The Immune-pineal axis: The role of pineal and extra-pineal melatonin in modulating inflammation. Advances in neuroimmune biology, 1 (1), 95–104.
  • Masana, M.I., et al., 2002. MT(2) melatonin receptors are present and functional in rat caudal artery. The journal of pharmacology and experimental therapeutics, 302 (3), 1295–1302.
  • Matteo, S., 1987. The effect of job stress and job interdependency on menstrual cycle length, regularity and synchrony. Psychoneuroendocrinology, 12 (6), 467–476.
  • McArthur, A.J., Gillette, M.U., and Prosser, R.A., 1991. Melatonin directly resets the rat suprachiasmatic circadian clock in vitro. Brain research, 565 (1), 158–161.
  • McClintock, M.K., 1971. Menstrual synchorony and suppression. Nature, 229 (5282), 244–245.
  • Mediavilla, M.D., Cos, S., and Sánchez-Barceló, E.J., 1999. Melatonin increases p53 and p21WAF1 expression in MCF-7 human breast cancer cells in vitro. Life sciences, 65 (4), 415–420.
  • Migaud, M., et al., 2010. Emerging new sites for adult neurogenesis in the mammalian brain: a comparative study between the hypothalamus and the classical neurogenic zones. The European journal of neuroscience, 32 (12), 2042–2052.
  • Mohammadi, M.R., et al., 2012. Melatonin effects in methylphenidate treated children with attention deficit hyperactivity disorder: a randomized double blind clinical trial. Iranian journal of psychiatry, 7 (2), 87–92.
  • Morera-Fumero, A.L., and Abreu-Gonzalez, P., 2013. Role of melatonin in schizophrenia. International journal of molecular sciences, 14 (5), 9037–9050.
  • Morgan, P., et al., 1994. Melatonin receptors: Localization, molecular pharmacology and physiological significance. Neurochemistry international, 24 (2), 101–146.
  • Muxel, S.M., et al., 2012. NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene. Plos one, 7 (12), e52010.
  • Nagorny, C., and Lyssenko, V., 2012. Tired of diabetes genetics? Circadian rhythms and diabetes: the MTNR1B story? Current diabetes reports, 12 (6), 667–672.
  • Nakade, O., et al., 1999. Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. Journal of pineal research, 27 (2), 106–110.
  • Nichols, D.E., 2018. N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of psychopharmacology (Oxford, England), 32 (1), 30–36.
  • Niles, L.P., et al., 2004. Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers. BMC neuroscience, 5, 41
  • Nölte, I., et al., 2009. Pineal volume and circadian melatonin profile in healthy volunteers: an interdisciplinary approach. Journal of magnetic resonance imaging, 30 (3), 499–505.
  • Nordlund, J.J., and Lerner, A.B., 1977. The effects of oral melatonin on skin color and on the release of pituitary hormones. The journal of clinical endocrinology and. metabolism, 45 (4), 768–774.
  • Nosjean, O., et al., 2000. Identification of the melatonin-binding site MT3 as the quinone reductase 2. The journal of biological chemistry, 275 (40), 31311–31317.
  • O’Collins, V.E., et al., 2011. Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing. Journal of cerebral blood flow and metabolism : official journal of the international society of cerebral blood flow and metabolism, 31 (3), 962–975.
  • Obayashi, K., Saeki, K., and Kurumatani, N., 2014. Association between urinary 6-sulfatoxymelatonin excretion and arterial stiffness in the general elderly population: The HEIJO-KYO cohort. The journal of clinical endocrinology and metabolism, 99 (9), 3233–3239.
  • Ochoa-Sanchez, R., et al., 2011. Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand. The journal of neuroscience : the official journal of the society for neuroscience, 31 (50), 18439–18452.
  • Ochoa-Sanchez, R., et al., 2014. Melatonin, selective and non-selective MT1/MT2 receptors agonists: differential effects on the 24-h vigilance states. Neuroscience letters, 561, 156–161.
  • Olie, P., and Emsley, R., 2005. Confirmed clinical efficacy of agomelatine (25-50 mg) in major depression; two randomized, double-blind controlled studies. European journal of neuropsychopharmacology, 15 (3), S416.
  • Oren, M., 2003. Decision making by p53: Life, death and cancer. Cell death and differentiation, 10 (4), 431–442.
  • Ortiz, G.G., et al., 2017. Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson’s disease. Gaceta Medica de Mexico, 153 (Supl. 2), S72–S81.
  • Ostrin, L.A., 2019. Ocular and systemic melatonin and the influence of light exposure. Clinical and experimental optometry, 102 (2), 99–108.
  • Owino, S., et al., 2016. Melatonin signaling controls the daily rhythm in blood glucose levels independent of peripheral clocks. Plos one, 11 (1), e0148214.
  • Pacchierotti, C., et al., 2001. Melatonin in Psychiatric Disorders: A Review on the Melatonin Involvement in Psychiatry. Frontiers in neuroendocrinology, 22 (1), 18–32. doi:10.1006/frne.2000.0202
  • Paltsev, M.A., et al., 2016. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: Role and significance in aging. Oncotarget, 7 (11), 11972–11983.
  • Pandi-Perumal, S.R., et al., 2006. Melatonin: Nature's most versatile biological signal? The FEBS journal, 273 (13), 2813–2838.
  • Parameyong, A., et al., 2013. Melatonin attenuates methamphetamine-induced disturbances in mitochondrial dynamics and degeneration in neuroblastoma SH-SY5Y cells. Journal of pineal research, 55 (3), 313–323.
  • Pauley, S.M., 2004. Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue. Medical hypotheses, 63 (4), 588–596.
  • Pei, Z., Pang, S.F., and Cheung, R.T., 2003. Administration of melatonin after onset of ischemia reduces the volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model. Stroke, 34 (3), 770–775.
  • Petranka, J., et al., 1999. The oncostatic action of melatonin in an ovarian carcinoma cell line. Journal of pineal research, 26 (3), 129–136.
  • Pierpaoli, W., and Regelson, W., 1994. Pineal control of aging: Effect of melatonin and pineal grafting on aging mice. Proceedings of the national academy of sciences of the United States of America, 91 (2), 787–791.
  • Pires-Lapa, M.A., et al., 2013. Melatonin synthesis in human colostrum mononuclear cells enhances dectin-1-mediated phagocytosis by mononuclear cells. Journal of pineal research, 55 (3), 240–246.
  • Plant, T.M., and Zorub, D.S., 1986. Pinealectomy in agonadal infantile male rhesus monkeys (Macaca mulatta) does not interrupt initiation of the prepubertal hiatus in gonadotropin secretion. Endocrinology, 118 (1), 227–232.
  • Pontes, G.N., et al., 2006. Injury switches melatonin production source from endocrine (pineal) to paracrine (phagocytes) - melatonin in human colostrum and colostrum phagocytes. Journal of pineal research, 41 (2), 136–141.
  • Porfirio, M.C., et al., 2017. Can melatonin prevent or improve metabolic side effects during antipsychotic treatments? Neuropsychiatric disease and treatment, 13, 2167–2174.
  • Potter, G.D.M., et al., 2016. Circadian rhythm and sleep disruption: causes, metabolic consequences, and countermeasures. Endocrine reviews, 37 (6), 584–608.
  • Pu, Y., et al., 2007. High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging. American journal of neuroradiology, 28 (9), 1706–1709.
  • Puig-Domingo, M., et al., 1992. Brief report: melatonin-related hypogonadotropic hypogonadism. The New England journal of medicine, 327 (19), 1356–1359.
  • Quay, W.B., 1970. Precocious entrainment and associated characteristics of activity patterns following pinalectomy and reversal of photoperiod. Physiology and behavior, 5 (11), 1281–1290.
  • Radogna, F., Diederich, M., and Ghibelli, L., 2010. Melatonin: a pleiotropic molecule regulating inflammation. Biochemical pharmacology, 80 (12), 1844–1852.
  • Ramirez-Rodriguez, G., et al., 2009. Melatonin modulates cell survival of new neurons in the hippocampus of adult mice. Neuropsychopharmacology : official Publication of the American College of Neuropsychopharmacology, 34 (9), 2180–2191.
  • Ramirez-Rodriguez, G., et al., 2011. Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. Journal of pineal research, 50 (1), 29–37.
  • Ramirez-Rodriguez, G.B., et al., 2018. Melatonin influences structural plasticity in the axons of granule cells in the dentate gyrus of Balb/C mice. International journal of molecular sciences, 20 (1), 73.
  • Rasmussen, D.D., et al., 1999. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology, 140 (2), 1009–1012.
  • Rawashdeh, O., et al., 2007. Melatonin suppresses nighttime memory formation in zebrafish. Science (New York, N.Y.).), 318 (5853), 1144–1146.
  • Rawashdeh, O., and Maronde, E., 2012. The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing. Frontiers in molecular neuroscience, 5, 27.
  • Reiter, R.J., et al., 1999. Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mechanisms of ageing and development, 110 (3), 157–173.
  • Reiter, R.J., Tan, D.X., and Galano, A., 2014. Melatonin: exceeding expectations. Physiology (Bethesda, Md.).), 29 (5), 325–333.
  • Reiter, R.J., et al., 2007. Medical implications of melatonin: receptor-mediated and receptorindependent actions. Advances in medical science, 52, 11–28.
  • Reiter, R.J., 1991. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine reviews, 12 (2), 151–180.
  • Reiter, R.J., 1993. The melatonin rhythm: both a clock and a calendar. Experientia, 49 (8), 654–859.
  • Reiter, R.J., 1998. Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. Nutrition (Burbank, Los Angeles County, Calif.).), 14 (9), 691–696.
  • Reppert, S.M., et al., 1995. Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mel1b melatonin receptor. Proceedings of the national academy of sciences of the United States of America, 92 (19), 8734–8738.
  • Reppert, S.M., and Weaver, D.R., 2001. Molecular analysis of mammalian circadian rhythms. Annual review of physiology, 63, 647–676.
  • Revell, V.L., et al., 2006. Advancing human circadian rhythms with afternoon melatonin and morning intermittent bright light. Journal of clinical endocrinology and metabolism, 91 (1), 54–59.
  • Reybier, K., et al., 2011. Insights into the redox cycle of human quinone reductase 2. Free radical research, 45 (10), 1184–1195.
  • Rojansky, N., Brzezinski, A., and Schenker, J.G., 1992. Seasonality in human reproduction: an update. Human reproduction (Oxford, England)), 7 (6), 735–745.
  • Rojczyk-Gołębiewska, E., Pałasz, A., and Wiaderkiewicz, R., 2014. Hypothalamic subependymal niche: a novel site of the adult neurogenesis. Cellular and molecular neurobiology, 34 (5), 631–642.
  • Rosales-Corral, S., et al., 2003. Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and E. Journal of pineal research, 35 (2), 80–84.
  • Rosales-Corral, S.A., et al., 2012. Alzheimer's disease: pathological mechanisms and the beneficial role of melatonin. Journal of pineal research, 52 (2), 167–202.
  • Roskoski, R., Jr. 2016. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacological research, 107, 249–275.
  • Roth, J.A., et al., 1999. Melatonin promotes osteoblast differentiation and bone formation. The journal of biological chemistry, 274 (31), 22041–22047.
  • Roy, D., and Belsham, D.D., 2002. Melatonin receptor activation regulates GnRH gene expression and secretion in GT1-7 GnRH neurons. Signal transduction mechanisms. The journal of biological chemistry, 277 (1), 251–258.
  • Sabatini, R.A., et al., 2008. ACE activity is modulated by kinin B2 receptor. Hypertension (Dallas, Tex. : 1979)), 51 (3), 689–695.
  • Sack, R.L., et al.,; American Academy of Sleep Medicine. 2007. Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review. Sleep, 30 (11), 1484–1501.
  • Sadat-Ali, M., Habdan, I., and Othman, A., 2000. Adolescent idiopathic scoliosis. Is low melatonin a cause?. Joint bone spine, 67, 62–64.
  • Sadeh, A., 1997. Sleep and melatonin in infants: a preliminary study. Sleep, 20 (3), 185–191.
  • Samuel, D.S., Duraisamy R., and Kumar, M., 2018. Pineal gland - A mystic gland. Drug invention today, 11 (1), 55–58.
  • Sanchez-Barcelo, E.J., et al., 2017. Clinical uses of melatonin in neurological diseases and mental and behavioural disorders. Current medicinal chemistry, 24 (35), 3851–3878.
  • Santoro, R., et al., 2012. Melatonin triggers p53Ser phosphorylation and prevents DNA damage accumulation. Oncogene, 31 (24), 2931–2942.
  • Sapède, D., and Cau, E., 2013. The pineal gland from development to function. Current topics in developmental biology, 106, 171–215. doi:10.1016/B978-0-12-416021-7.00005-5
  • Saper, C.B., et al., 2005. The hypothalamic integrator for circadian rhythms. Trends in neurosciences, 28 (3), 152–157.
  • Saxvig, I.W., et al., 2014. A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep. Chronobiology international, 31 (1), 72–86.
  • Scheer, F.A., et al., 2012. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep, 35 (10), 1395–1402.
  • Scheer, F.A., et al., 2004. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension (Dallas, Tex.: 1979)), 43 (2), 192–197.
  • Scheer, F.A., 2005. Potential use of melatonin as adjunct antihypertensive therapy. American journal of hypertension, 18 (12 Pt 1), 1619–1620.
  • Schernhammer, E.S., et al., 2003. Night-shift work and risk of colorectal cancer in the nurses' health study. Journal of the National Cancer Institute, 95 (11), 825–828.
  • Sharma, V.K., and Chandrashekaran, M.K., 2005. Zeitgebers (time cues) for biological clocks. Current science, 89 (7), 1136–1146.
  • Shechter, A., et al., 2012. Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder. Sleep medicine, 13 (8), 1071–1078.
  • Silman, R., 1991. Melatonin and the human gonadotrophin-releasing hormone pulse generator. The journal of endocrinology, 128 (1), 7–11.
  • Silva, S.O., et al., 2004. Neutrophils as a specific target for melatonin and kynuramines: Effects on cytokine release. Journal of neuroimmunology, 156 (1-2), 146–152.
  • Sinha, B.R., et al., 2014. A comparative study indicates methimazole induced chemical hypothyroidism causes inhibition of pineal gland karyomorphology in three different species of animals. International journal of pure and applied zoology, 2, 84–94.
  • Skwarlo-Sonta, K., et al., 2003. Bidirectional communication between the pineal gland and the immune system. Canadian journal of physiology and pharmacology, 81 (4), 342–349.
  • Slawik, H., et al., 2016. Prospective Study on Salivary Evening Melatonin and Sleep before and after Pinealectomy in Humans. Journal of biological rhythms, 31 (1), 82–93.
  • Sletten, T.L., et al.,; for the Delayed Sleep on Melatonin (DelSoM) Study Group. 2018. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: a double-blind, randomised clinical trial. PLOS Medicine, 15 (6), e1002587.
  • Smith, J.A., O'Hara, J., and Schiff, A.A., 1981. Altered diurnal serum melatonin rhythm in blind men. Lancet (London, England), 2 (8252), 933.
  • Smith, M.R., Fogg, L.F., and Eastman, C.I., 2009. Practical interventions to promote circadian adaptation to permanent night shift work: study 4. Journal of biological rhythms, 24 (2), 161–172.
  • Song, J., 2019. Pineal gland dysfunction in Alzheimer's disease: relationship with the immune-pineal axis, sleep disturbance, and neurogenesis. Molecular neurodegeneration, 14 (1), 28
  • Soto-Vega, E., et al., 2004. Melatonin stimulates calmodulin phosphorylation by protein kinase C. Journal of pineal research, 37 (2), 98–106. doi:10.1111/j.1600-079X.2004.00141.x
  • Spitzer, R.L., et al., 1999. Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial. American journal of psychiatry, 156, 1392–1396.
  • Srinivasan, V., et al., 2010. Melatonin and its agonist ramelteon in Alzheimer's disease: possible therapeutic value. International journal of Alzheimer's disease, 2011, 741974
  • Srinivasan, V., et al., 2005. Role of melatonin in neurodegenerative diseases. Neurotoxicity research, 7 (4), 293–318.
  • Srinivasan, V., et al., 2006. Melatonin in mood disorders. World journal of biological psychiatry, 7 (3), 138–151.
  • Stevens, R. G., 2004. Epidemiological evidence on artificial lighting patterns and risk of breast cancer. Final Report. The Fifth International LRO Lighting Research Symposium, Light and Human Health, November 3–5, 2002. Report No. 1009370. Palo Alto, CA: The Electric Power Research Institute.
  • Straif, K., et al.,; WHO International Agency For Research on Cancer Monograph Working Group. 2007. Carcinogenicity of shift-work, painting, and fire-fighting. The lancet oncology, 8 (12), 1065–1066.
  • Su, S.C., et al., 2017. Cancer metastasis: mechanisms of inhibition by melatonin. Journal of pineal research, 62, 12370.
  • Sun, X., et al., 2016. The potential role of melatonin on mental disorders: insights from physiology and pharmacology. Bipolar disorder: open access, 2 (1). doi:10.4172/2472-1077.1000105
  • Suofu, Y., et al., 2017. Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proceedings of the national academy of sciences of the United States of America, 114 (38), E7997–E8006. doi:10.1073/pnas.1705768114
  • Tamarkin, L., et al., 1981. Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat. Cancer research, 41 (11 Pt 1), 4432–4436.
  • Tamura, E.K., Silva, C.L., and Markus, R.P., 2006. Melatonin inhibits endothelial nitric oxide production in vitro. Journal of pineal research, 41 (3), 267–274.
  • Tan, D.X., et al., 2016. Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics. International journal of molecular sciences, 17 (12), 2124.
  • Tan, D.X., et al., 2007. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of pineal research, 42 (1), 28–42.
  • Tan, D.X., et al., 2018. Pineal calcification, melatonin production, aging, associated health consequences and rejuvenation of the pineal gland. Molecules, 23 (2), 301. pii:
  • Tapp, E., 1979. The histology and pathology of the human pineal gland. Progress in brain research, 52, 481–500.
  • Tchekalarova, J., et al., 2016. Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats. Behavioural brain research, 302, 11–28.
  • Tocharus, C., et al., 2014. Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor. Neuroscience, 275, 314–321.
  • Toh, K.L., 2008. Basic science review on circadian rhythm biology and circadian sleep disorders. Annual academic medicine (Singapore), 37 (8), 662–668.
  • Tordjman, S., et al., 2005. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biological psychiatry, 57 (2), 134–138.
  • Tordjman, S., et al., 2017. Melatonin: pharmacology, functions and therapeutic benefits. Current neuropharmacology, 15 (3), 434–443.
  • Tordjman, S., et al., 2013. Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives. International journal of molecular sciences, 14 (10), 20508–20542.
  • Tuomi, T., et al., 2016. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell metabolism, 23 (6), 1067–1077.
  • Turgut, A.T., et al., 2008. Age-related changes in the incidence of pineal gland calcification in Turkey: A prospective multicenter CT study. Pathophysiology, 15 (1), 41–48.
  • Unger, T., et al., 1999. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. The EMBO journal, 18 (7), 1805–1814.
  • Van Geijlswijk, I.M., Korzilius, H., and Smits, M.G., 2010. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep, 33 (12), 1605–1614.
  • Vandewalle, G., et al., 2007. Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod. Journal of sleep research, 16 (2), 148–155.
  • Varma, A., et al., 2002. The effect of antidepressants on serum melatonin levels in endogenous depression. Journal of association of physicians India, 50, 1262–1265.
  • Vinogradova, I.A., et al., 2010. Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in young but not in old rats. Aging, 2 (2), 82–92.
  • Voordouw, B.C., et al., 1992. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. The journal of clinical endocrinology and metabolism, 74 (1), 108–117.
  • Waly, N.E., and Hallworth, R., 2015. Circadian pattern of melatonin MT1 and MT2 receptor localization in the rat suprachiasmatic nucleus. Journal of circadian rhythms, 13, 1–7.
  • Wang, X.C., et al., 2008. Effect of melatonin and melatonylvalpromide on beta-amyloid and neurofilaments in N2a cells. Neurochemical research, 33 (6), 1138–1144.
  • Wei, J.Y., et al., 2015. Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation. Journal of pineal research, 58 (4), 429–438.
  • Weishaupt, J.H., et al., 2006. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. Journal of pineal research, 41 (4), 313–323.
  • Welsh, D.K., Takahashi, J.S., and Kay, S.A., 2010. Suprachiasmatic nucleus: cell autonomy and network properties. Annual review of physiology, 72, 551–577.
  • Westermann, J., et al., 2015. System consolidation during sleep - a common principle underlying psychological and immunological memory formation. Trends in neurosciences, 38 (10), 585–597.
  • Wideman, C.H., and Murphy, H.M., 2009. Constant light induces alterations in melatonin levels, food intake, feed efficiency, visceral adiposity, and circadian rhythms in rats. Nutritional neuroscience, 12 (5), 233–240.
  • Wilson, H.C., Kiefhaber, S.H., and Gravel, V., 1991. Two studies of menstrual synchrony: negative results. Psychoneuroendocrinology, 16 (4), 353–359.
  • Witt-Enderby, P.A., et al., 2000. Melatonin induction of filamentous structures in non-neuronal cells that is dependent on expression of the human mt1 melatonin-receptor. Cell motility and the cytoskeleton, 46 (1), 28–42.
  • Wu, J.-H., et al., 2016. Effect of melatonin and calmodulin in an Idiopathic Scoliosis Model. BioMed research international, 2016, 8460291. doi:10.1155/2016/8460291
  • Xie, S., et al., 2015. Melatonin protects against chronic intermittent hypoxia-induced cardiac hypertrophy by modulating autophagy through the 5' adenosine monophosphate-activated protein kinase pathway. Biochemical and Biophysical Research Communication, 464 (4), 975–981.
  • Xie, Z., et al., 2017. A review of sleep disorders and melatonin. Neurological research, 39 (6), 559–565.
  • Yang, Y., et al., 2017. Up-regulation of miR-325-3p suppresses pineal aralkylamine N-acetyltransferase (Aanat) after neonatal hypoxia-ischemia brain injury in rats . Brain Research, 1668, 28–35.
  • Yeung, H.M., et al., 2015. Cardioprotective effects of melatonin against myocardial injuries induced by chronic intermittent hypoxia in rats. Journal of pineal research, 58 (1), 12–25.
  • Zacharias, L., and Wurtman, R.J., 1964. Blindness: its relation to age of menarche. Science (New York, N.Y.)), 144 (3622), 1154–1155.
  • Zawilska, J.B., Skene, D.J., and Arendt, J., 2009. Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacological reports, 61 (3), 383–410.
  • Zee, P.C., and Goldstein, C.A., 2010. Treatment of shift work disorder and jet lag. Current treatment options in neurology, 12 (5), 396–411.
  • Zeitzer, J.M., et al., 2000. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. The journal of physiology, 526 (3), 695–702.
  • Zhang, W., et al., 2016. Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials. Neurological sciences : official journal of the Italian neurological society and of the Italian society of clinical neurophysiology, 37 (1), 57–65.
  • Zhao, D., et al., 2019. Melatonin synthesis and function: evolutionary history in animals and plants. Frontiers in endocrinology, 10, 249.
  • Zhdanova, I., Lynch, H., and Wurtman, R., 1997. Melatonin: a sleeppromoting hormone. Sleep, 20, 899–907.
  • Zhdanova, I.V., et al., 1995. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clinical pharmacology therapy, 57 (5), 552–558.
  • Zhou, J.N., et al., 2003. Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. Journal of pineal research, 35 (2), 125–130.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.