• The Korean Journal of Zoology
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• v.39 no.4
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• pp.337-351
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• 1996

Melatonin Is a multifunctional hormone secreted from the pineal gland in the middle of cerebrum and cerebellum. Its synthesis and release reflect photopedod;Photopedod is a yearly predictable ambient factor that most animals utilize as an environmental cue for maximum survival. Hamsters maintaln reproductive activity in summer during which day length exceeds night time. Upon the advent of autumnal equinox they undergo gonadal regression. The photoperiodic effects are prevented by removal of the pineal gland and restored by the timed repiacument of melatonin. The results suggest that melatonin constitutes part of control mechanism whereby environmental information is transduced to neuroendocrine signal responsIble for the functional integrity of the reproductive system. From the studies for the action site of melatonin following the treatment of photopedod or melatonin in the lesion of a spedflc portion of hypothalamus, suprachiasmatic nuclei and pars tuberalis are shown to be a consensus site for melatonIn. The action of melatonin. In the regulation of reproduction is largely unknown. It is mainly due to the lack of acute effect of melatonin on gonadotropin secretion. However, reduction of the gonadotropln release and augmentation of the hypothalamic gonadotropin-releasing hormone (GnRH) content by long-term treatment of melatonln Indicate that constant presence of melatonln may partidpate in the regulation of sexual activity via the GnRH neuronal system. The action mechanism by which melatonin exerts Its effect on GnRH neuron needs to be eluddated. The inability of opiold analogues to affect the reproductive hormones in sexually regressed animals by inhibftory photopedod and melatonin suggests that the opioldergic neuron may be a prime intervening mediator. Recent cloning of melatonin receptor will contribute to investigate its anatomical Identification and the action mechanism of melatonin on target tissues at the molecular level.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.13.1-13.15
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• 2018

Wound healing is delayed in diabetic patients. Increased apoptosis and endothelial progenitor cell (EPC) dysfunction are implicated in delayed diabetic wound healing. Melatonin, a major secretory product of the pineal gland, promotes diabetic wound healing; however, its mechanism of action remains unclear. Here, EPCs were isolated from the bone marrow of mice. Treatment of EPCs with melatonin alleviated advanced glycation end product (AGE)-induced apoptosis and cellular dysfunction. We further examined autophagy flux after melatonin treatment and found increased light chain 3 (LC3) and p62 protein levels in AGE-treated EPCs. However, lysosome-associated membrane protein 2 expression was decreased, indicating that autophagy flux was impaired in EPCs treated with AGEs. We then evaluated autophagy flux after melatonin treatment and found that melatonin increased the LC3 levels, but attenuated the accumulation of p62, suggesting a stimulatory effect of melatonin on autophagy flux. Blockage of autophagy flux by chloroquine partially abolished the protective effects of melatonin, indicating that autophagy flux is involved in the protective effects of melatonin. Furthermore, we found that the AMPK/mTOR signaling pathway is involved in autophagy flux stimulation by melatonin. An in vivo study also illustrated that melatonin treatment ameliorated impaired wound healing in a streptozotocin-induced diabetic wound healing model. Thus, our study shows that melatonin protects EPCs against apoptosis and dysfunction via autophagy flux stimulation and ameliorates impaired wound healing in vivo, providing insight into its mechanism of action in diabetic wound healing.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5835-5842
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• 2015

Background: Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms. Materials and Methods: The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38). Results: The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38. Conclusions: Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.

• Journal of Dairy Science and Biotechnology
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• v.34 no.1
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• pp.37-41
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• 2016

Melatonin is a hormone produced by the pineal gland in dark conditions. It plays a major role in the regulation of the sleep-wake cycle. Melatonin synthesis is known to be suppressed by environmental light. Cortisol is a steroid hormone that is a major indicator of physiological alterations due to stressful stimuli. It also displays a circadian rhythm, like melatonin. The highest levels are encountered during early morning and the lowest levels are observed at around midnight. In the present study, the effects of milking time on the melatonin and cortisol concentrations of raw milk and milk powder at the summer and winter solstices were examined. The melatonin concentration in milk increased significantly if cows were milked in the dark at night (p<0.05). The melatonin concentration in milk powder showed the same pattern with respect to the milking time (p<0.05). However, no significant difference in the cortisol concentration was observed between day- and night-time milk. Although the time of day did not affect the level of milk cortisol, seasonal factors affected the release of cortisol in milk (p<0.05). In conclusion, night-time milk is rich in endogenous melatonin. In this respect, it has potential applications for the development of melatonin rich-dairy products, which serve as natural sources of melatonin.

• Journal of Marine Life Science
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• v.8 no.1
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• pp.32-42
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• 2023

Fish reproduction is regulated by various neurohormones secreted from the brain and gonadotropic hormones secreted from the pituitary. Reproduction of eel (Anguilla japonica) is also regulated by these hormones. However, how the neurohormones regulate the secretion of pituitary hormones during sexual maturation is not completely understood. Previous studies have shown that neurohormones such as progesterone (P4), melatonin and serotonin (5-HT) are involved in the regulation of reproductive processes in some fish. In this study, the eel pituitary was primary cultured, and stabilized pituitary cells were treated with P4, 17β-estradiol (E2), melatonin, or 5-HT. The effect of these treatments on the expression of FSHβ, LHβ, GH and SL mRNA was, then, investigated. P4 increased the expression of FSHβ and LHβ in pituitary cells, and melatonin increased the expression of GH and SL as well as FSHβ and LHβ. However, 5-HT did not significantly affect the expression of these mRNA. These results suggest that P4 and melatonin may play some important roles in the early sexual maturation of eels.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.389-398
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• 2018

p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol. We found that p-cresol concentration-dependently reduced proliferation of mesenchymal stem cells. Pretreatment with melatonin prevented pro-senescence effects of p-cresol on mesenchymal stem cells. We found that by inducing phosphorylation of Akt and activating the Akt signaling pathway, melatonin enhanced catalase activity and thereby inhibited the accumulation of reactive oxygen species induced by p-cresol in mesenchymal stem cells, ultimately preventing abnormal activation of autophagy. Furthermore, preincubation with melatonin counteracted other pro-senescence changes caused by p-cresol, such as the increase in total 5'-AMP-activated protein kinase expression and decrease in the level of phosphorylated mechanistic target of rapamycin. Ultimately, we discovered that melatonin restored the expression of senescence marker protein 30, which is normally suppressed because of the induction of the autophagy pathway in chronic kidney failure patients by p-cresol. Our findings suggest that stem cell senescence in patients with chronic kidney failure could be potentially rescued by the administration of melatonin, which grants this hormone a novel therapeutic role.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.91-97
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• 2017

Although anti-aging activities of melatonin, a hormone secreted by the pineal gland, have been reported in senescence-accelerated mouse models and several types of cells, its impact and mechanism on the senescence of human dental pulp cells (HDPCs) remains unknown. In this study, we examined the impact of melatonin on cellular premature senescence of HDPCs. Here, we found that melatonin markedly inhibited senescent characteristics of HDPCs after exposure to hydrogen peroxide ($H_2O_2$), including the increase in senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal)-positive HDPCs and the upregulation of p21 protein, an indicator for senescence. In addition, as melatonin attenuated $H_2O_2$-stimulated phosphorylation of c-Jun N-terminal kinase (JNK), while selective inhibition of JNK activity with SP600125 significantly attenuated $H_2O_2$-induced increase in SA-beta-gal activity. Results reveal that melatonin antagonizes premature senescence of HDPCs via JNK pathway. Thus, melatonin may have therapeutic potential to prevent stress-induced premature senescence, possibly correlated with development of dental pulp diseases, and to maintain oral health across the life span.

• Development and Reproduction
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• v.17 no.1
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• pp.45-53
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• 2013

The action of melatonin within the body of animals is known to be mediated by melatonin receptors. Three different types of melatonin receptors have been identified so far in fish. However, which of these are specifically involved in puberty onset is not known in fish. We cloned and analyzed the sequence of melatonin receptor 1a (mel 1a) gene in Nile tilapia Oreochromis niloticus. In addition, we examined the tissue distribution of gene expressions for three types of receptors, mel 1a, 1b and lc and investigated which of them is involved in the onset of puberty by comparing their expression with that of gonadotropin-releasing hormone receptor I (GnRHr I) gene using quantitative real-time PCR from 1 week post hatch (wph) to 24 wph. The mel 1a gene of Nile tilapia consisted of two exons and one bulky intron between them. Mel 1a gene was found to be highly conserved gene showing high homology with the corresponding genes from different teleost. All three types of melatonin receptor genes were expressed in the brain, eyes and ovary in common. Expression of mel 1a gene was the most abundant and ubiquitous among 3 receptors in the brain, liver, gill, ovary, muscle, eye, heart, intestine, spleen and kidney. Mel 1b and mel 1c genes were, however, expressed in fewer tissues at low level. During the development post hatch, expressions of both mel 1a and GnRHr I genes significantly increased at 13 wph which was close to the putative timing of puberty onset in this species. These results suggest that among three types of receptors mel 1a is most likely associated with the action of melatonin in the onset of puberty in Nile tilapia.

• Journal of Environmental Health Sciences
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• v.30 no.3
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• pp.191-206
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• 2004

The present study investigated the hypothesis that a extremely low frequency magnetic field partially suppresses the synthesis of melatonin in a group of 28 primary schoolchildren living nearby and 60 primary schoolchildren aged 12 years living far away from overhead transmission power lines from December 2003 to April 2004 in Seoul, Korea. The mean personal exposure levels of the primary schoolchildren living nearby overhead transmission power line were 0.37 ${\mu}$T, whereas the value for the primary schoolchildren living away from overhead transmission power line 0.05 mT. From simple analyses, the mean melatonin levels in the primary schoolchildren living nearby were lower than away from overhead transmission power line, but not statistically significant differences in the levels of the melatonin (p=0.2421), whereas the statistically significant differences in the levels of the melatonin related to the distance from residence to power line less and more than 100 m by cut-off point (p=0.0139). In multiple linear regression analyses, distance from residence to power line (p=0.0146) and dietary habit about burned meat (p=0.0170) proved to be significant risk factors in the mean nocturnal melatonin levels in the primary schoolchildren. In conclusion, these results demonstrate that urinary levels of nocturnal melatonin are not altered in primary schoolchildren exposed to extremely low frequency magnetic field(ELF-MF) at overhead transmission power line.

• Development and Reproduction
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• v.24 no.4
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• pp.263-275
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• 2020

The proper administration of melatonin has well been documented to induce testicular regression in seasonal breeding animals. The subcutaneous injections of melatonin in the afternoon, not in the morning, consistently occurred testicular involution in the male Syrian (golden) hamsters whose reproductive activity is regulated by the photoperiod. But the effects of daily melatonin via gavage have not been estimated. Golden hamsters housed in long photoperiod (LP) were divided into 5 groups: the control animals housed in LP or in short photoperiod (SP) and animals treated daily with low (15 ㎍), middle (150 ㎍), and high dosages (1,500 ㎍) of pure melatonin by using gavage in the evening for 8 weeks. As results, LP control animals had large testes and SP controls displayed small and entirely regressed testes. The animals treated with various dosages of melatonin showed collectively degenerating effects on the weights of testes, epididymides, and seminal vesicles in the middle and high dosage groups, with the individual differences as well. The high dosages induced testicular regression in more proportion than the middle dosages did. The low dosage had large testes like the LP control animals. The small and inactive testes shown in some animals of both middle and high groups presented the complete regression as those of the animals maintained in SP. These results strongly suggest that the administrations of melatonin lead to testicular involution in the male golden hamsters when it is administered through gavage.