褪黑激素及其对动物生殖影响的研究进展

褪黑激素是由松果腺分泌的一种激素,在动物的生殖、生物钟、免疫、抗自由基等方面都有重要影响。简要综述了褪黑激素的主要理化性质及其生物学功能、褪黑激素受体,并总结了近年来褪黑激素对动物生殖影响的研究进展。     

HPLC法测定黄芩叶、花、种子中褪黑激素的含量

应用高效液相色谱荧光检测系统测定了昼夜两个时间点黄芩鲜叶中褪黑激素的浓度 差别,同时也检测了花、种子中褪黑激素的含量。结果表明,夜间和白天采集的新鲜叶片昼夜含量不同,分别为1.6503 ng/g和0.5163 ng/g。在花和种子中也检测到褪黑激素。尽管目前对褪黑激素在植物中的作用尚不完全清楚,但是有关植物中褪黑激素含量的研究将对营养、医药和农业等提供有益的信息。     

HPLC法测定黄芩叶、花、种子中褪黑激素的含量

应用高效液相色谱—荧光检测系统测定了昼夜两个时间点黄芩鲜叶中褪黑激素的浓度差别,同时也检测了花、种子中褪黑激素的含量。结果表明,夜间和白天采集的新鲜叶片昼夜含量不同,分别为1.6503ng/g和0.5163ng/g。在花和种子中也检测到褪黑激素。尽管目前对褪黑激素在植物中的作用尚不完全清楚,但是有关植物中褪黑激素含量的研究将对营养、医药和农业等提供有益的信息。     

低温胁迫下褪黑激素对烟草悬浮细胞精氨酸脱羧酶活性的影响

研究了褪黑激素对烟草(Nicotiana tabacum)悬浮细胞在低温胁迫下精氨酸脱羧酶活性及细胞生存率的影响。发现褪黑激素可以明显提高低温胁迫下烟草悬浮细胞精氨酸脱羧酶的活性, 并明显提高细胞的生存率。表明褪黑激素可能在低温条件下通过调节植物细胞内多胺的合成而提高抵御冷害的能力。     

低温胁迫下褪黑激素对烟草悬浮细胞精氨酸脱羧酶活性的影响

研究了褪黑激素对烟草(Nicotiana tabacum)悬浮细胞在低温胁迫下精氨酸脱羧酶活性及细胞生存率的影响.发现褪黑激素可以明显提高低温胁迫下烟草悬浮细胞精氨酸脱羧酶的活性,并明显提高细胞的生存率.表明褪黑激素可能在低温条件下通过调节植物细胞内多胺的合成而提高抵御冷害的能力.     

MT1受体在无蹼壁虎肝脏的分布

目的为观察褪黑激素受体1(melatoninreceptor1,MT1)免疫反应在无蹼壁虎肝脏分布。方法我们采用苏木素染色和免疫荧光单标的方法。结果发现无蹼壁虎肝脏主要由肝细胞和肝脏库普弗细胞组成;肝细胞单位区域细胞数右叶(rightlobe)(217·159±3·571个/mm2)较左叶(84·317±2·072个/mm2)明显多(P<0·05),库普弗细胞单位区域细胞数左叶(leftlobe)(50·276±2·257个/mm2)较右叶(18·241±1·563个/mm2)明显多(P<0·05);左、右叶库普弗细胞数占细胞总数的百分率明显不同(左叶:4·054%±1·642%,右叶:1·261%±0·536%)(P<0·05)。免疫组化结果显示MT1受体在肝细胞和库普弗细胞均有表达。MT1免疫阳性反应主要位于细胞膜和细胞质。MT1受体阳性反应肝细胞单位区域细胞数右叶(72·381±3·614细胞数/mm2)较左叶(38·153±2·684细胞数/mm2)明显多(P<0·05);库普弗细胞阳性反应单位区域细胞数左叶(12·541±0·572细胞数/mm2)较右叶(6·443±0·761细胞数/mm2)明显多(P<0·05)。MT1受体阳性反应细胞数在左、右叶库普弗细胞也存在明显的部位差异(P<0·05)。结论上述结果提示褪黑激素经褪黑激素受体的介导对无蹼壁虎肝脏左、右叶肝细胞和库普弗细胞生理功能的调控存在差异。     

夜间光照对褪黑激素抑制的量化计算

作为人体的重要激素之一,褪黑激素具备重要的生理功能．不适当的夜间光照会造成人体生物钟节律的异常,进而导致褪黑激素内分泌的抑制．夜间光照引起的褪黑激素抑制与光的波长和色温关系密切．此前尚仍缺乏一个夜间光照对褪黑激素抑制效果的量化计算方案．提出了一种夜间光照对褪黑激素抑制的量化算法,拟合了人体血液褪黑激素抑制率的相对光谱灵敏度归一化曲线,建立了夜间光照与褪黑激素抑制量化计算的算法模型．研究结果为室内安全光照环境的设计提供了理论依据和计算方法,并可在光污染的控制、夜间安全环境照明标准的制定等方面得到应用．     

季节变化因子对动物产热的影响

本文探讨了光周期和褪黑激素（ＭＬＴ）对动物适应性产热的影响,例证了光周期和褪黑激素二者都能增加动物的产热,但其调节产热具有动物的种属差异性。文章还讨论了光周期和ＭＬＴ调控产热的可能机制,并提出了有待深入研究的问题。     

褪黑激素对绒山羊皮肤中毛囊周期相关miRNAs表达模式的影响

褪黑激素(Melatonin, MT)和miRNAs在毛囊的生长发育过程中发挥重要的作用,但MT对绒山羊皮肤毛囊miRNAs表达模式的影响尚未见报道。为探索MT从miRNAs层次影响山羊绒生长的机制,文章在内蒙古绒山羊中实施了褪黑激素埋植试验：5只青年母羊作为实验组埋植褪黑激素,另外5只青年母羊作为对照。利用荧光定量 PCR 检测褪黑激素埋植前后毛囊周期相关 miRNAs 的表达变化。结果表明,埋植 MT 明显改变了6个绒毛相关 miRNAs的表达规律：在一个绒毛周期内,除 let-7a外,miR-203、miR-205、miR-96、miR-183和miR-199a的表达量均发生3次跃迁;埋植MT改变了miRNAs之间的共表达模式。对照组各miRNA之间相关系数范围为0.87~0.99(P<0.01)。与对照组相比,埋植组中 let-7a 与 miR-96、miR-199a、miR-205,miR-203与miR-96、miR-199a,miR-96与miR-183,miR-183与miR-199a之间的相关系数被明显消弱;MT通过下调6月份埋植组各miRNA的表达量提早诱发二次生绒。     

外源性褪黑激素对黄鳝性腺发育及性腺激素分泌的影响

通过注射实验研究了外源性褪黑激素对黄鲜性腺发育及性腺激素分泌的影响。结果表明,处于不同性腺发育时期的黄鲜对餐源褪黑激素的反应存在季节性差异。上述结果暗示,黑激素影响黄鲜性腺发育的关键时间可能是在性腺静止期,亦即Ⅳ期或／和Ⅳ期之前。     

Melatonin metabolism,signaling and possible roles in plants

Melatonin is a multifunctional biomolecule found in both animals and plants. In this review, the biosynthesis, levels, signaling, and possible roles of melatonin and its metabolites in plants is summarized. Tryptamine 5-hydroxylase (T5H), which catalyzes the conversion of tryptamine into serotonin, has been proposed as a target to create a melatonin knockout mutant presenting a lesion-mimic phenotype in rice. With a reduced anabolic capacity for melatonin biosynthesis and an increased catabolic capacity for melatonin metabolism, all plants generally maintain low melatonin levels. Some plants, including Arabidopsis and Nicotiana tabacum (tobacco), do not possess tryptophan decarboxylase (TDC), the first committed step enzyme required for melatonin biosynthesis. Major melatonin metabolites include cyclic 3-hydroxymelatonin (3-OHM) and 2-hydroxymelatonin (2-OHM). Other melatonin metabolites such as N¹-acetyl-N²-formyl-5-methoxykynuramine (AFMK), N-acetyl-5-methoxykynuramine (AMK) and 5-methoxytryptamine (5-MT) are also produced when melatonin is applied to Oryza sativa (rice). The signaling pathways of melatonin and its metabolites act via the mitogen-activated protein kinase (MAPK) cascade, possibly with Cand2 acting as a melatonin receptor, although the integrity of Cand2 remains controversial. Melatonin mediates many important functions in growth stimulation and stress tolerance through its potent antioxidant activity and function in activating the MAPK cascade. The concentration distribution of melatonin metabolites appears to be species specific because corresponding enzymes such as M2H, M3H, catalases, indoleamine 2,3-dioxygenase (IDO) and N-acetylserotonin deacetylase (ASDAC) are differentially expressed among plant species and even among different tissues within species. Differential levels of melatonin and its metabolites can lead to differential physiological effects among plants when melatonin is either applied exogenously or overproduced through ectopic overexpression.     

褪黑素与绵羊的季节性生殖

绵羊是一种短光照型生殖动物,具有明显的生殖季节性。人们普遍认为,绵羊生殖周期与环境光周期的同步变化是通过褪黑素作用于下丘脑－垂体－性腺轴系统来实现的。近年来的不少研究结果表明,绵羊对光周期的感受性还受褪黑素受体的调控。现从生态学（光周期的生殖效应）、神经内分泌学和分子生物学（褪黑素受体）等领域的研究进展出发,对褪黑素调控绵羊自然季节性生殖的作用及机制进行系统综述。     

Melatonin: A new inhibitor agent for cervical cancer treatment

Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms.     

Regulation effects of melatonin on bone marrow mesenchymal stem cell differentiation

Melatonin’s therapeutic potential has been highly underestimated because its biological functional roles are diverse and relevant mechanisms are complicated. Among the numerous biological activities of melatonin, its regulatory effects on pluripotent mesenchymal stem cells (MSCs), which are found in bone marrow stem cells (BMSCs) and adipose tissue (AD-MSC), have been recently proposed, which has received increasingly more attention in recent studies. Moreover, receptor-dependent and receptor-independent responses to melatonin are identified to occur in these cells by regulating signaling pathways, which drive the commitment and differentiation of MSCs into osteogenic, chondrogenic, or adipogenic lineages. Therefore, the aim of our current review is to summarize the evidence related to the utility of melatonin as a regulatory agent by focusing on its relationship with the differentiation of MSCs. In particular, we aimed to review its roles in promoting osteogenic and chondrogenic differentiation and the relevant signaling cascades involved. Also, the roles that melatonin and, particularly, its receptors play in these processes are highlighted.     

The effects of melatonin on neurohormonal regulation in cardiac cachexia: A mechanistic review

Heart failure (HF) is one of the prominent health concerns and its morbidity is comparable to many malignancies. Cardiac cachexia (CC), characterized by significant weight loss and muscle wasting, frequently occurs in progressive stage of HF. The pathophysiology of CC is multifactorial including nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic/catabolic imbalance. Neurohormones are critically involved in the development of both HF and CC. Melatonin is known as an anti-inflammatory and antioxidant hormone. It seems that melatonin possibly regulates the neurohormonal signaling pathway related to muscle wasting in CC, but limited comprehensive data is available on the mechanistic aspects of its activity. In this, we reviewed the reports regarding the role of neurohormones in CC occurrence and possible activity of melatonin in modulation of HF and subsequently CC via neurohormonal regulation. In addition, we have discussed proposed mechanisms of action for melatonin considering its possible interactions with neurohormones. In conclusion, melatonin likely regulates the signaling pathways related to muscle wasting in CC by reducing tumor necrosis factor α levels and activating the gene expression of insulin-like growth factor-1. Also, this hormone inhibits the proteolytic pathway by inhibiting nuclear factor-κB (NF-κB), renin-angiotensin system and forkhead box protein O1 pathways and could increase protein synthesis by activating Akt and mammalian target of rapamycin. To elucidate the positive role of melatonin in CC and exact mechanisms related to muscle wasting more cellular and clinical trial studies are needed.     

Melatonin is an appropriate candidate for breast cancer treatment: Based on known molecular mechanisms

Breast cancer is the most prevalent cancer and one of the most important causes of death in women throughout the world. Breast cancer risk factors include smoking, alcohol consumption, personal and family history, hypertension, and hormone therapy, long-term use of nonsteroidal anti-inflammatory drugs and tobacco usage. Surgery, chemotherapy, radiotherapy, immunotherapy, and neoadjuvant therapy are the current means for breast cancer treatment. Despite hormonal agents and chemotherapy, which have beneficial effects on lowering breast cancer death rate, the reaction of different people to these treatments is still a challenging point. Melatonin (N-acetyl-5-methoxy tryptamine) is a methoxy indole compound that is mainly secreted by the pineal gland at night; it is as an antioxidant, anti-inflammatory, and oncostatic agent. On the basis of recent studies, melatonin has antitumor properties on different cancer types and it may suppress cancer development in vitro and as well as in animal models. It is suggested that melatonin inhibits the development of breast cancer by various mechanisms. This paper summarizes the roles of melatonin in breast cancer treatment from the aspect of its molecular actions.     

The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1-40

Intraventricular infusion of rats with beta-amyloid for 14 days resulted in memory deficit in the water maze as well as decreases in choline acetyltransferase activities and somatostatin levels in the cerebral cortex and hippocampus. These changes were not altered by daily intraperitoneal injection of 20 mg/Kg melatonin. Orally administered Ginkgo biloba extract, however, partially reversed the memory deficit and the decrease in choline actyltransferase activities in the hippocampus. The latter treatment failed to reverse the decrease in somatostatin levels. The results indicate that orally administered Ginkgo biloba extract can protect the brain against beta-amyloid from changes leading to memory deficit through its effect on the cholinergic system.     

Melatonin increases tissue accumulation and toxicity of cadmium in the bank vole (<Emphasis Type="Italic">Clethrionomys glareolus</Emphasis>)

Recent study has shown that a short photoperiod increases the accumulation and toxicity of cadmium (Cd) in the bank vole as compared to a long photoperiod. Since many of the effects of photoperiod on physiological processes in small mammals are transduced by the pineal gland and its hormone melatonin, in this study the effect of subchronic melatonin injection (7 mol/kg/day for 6 weeks) on the hepatic, renal and intestinal Cd accumulation in the bank voles raised under a long photoperiod and exposed to dietary Cd (0.9 mol/g) was examined. Simultaneously, histological examinations of the liver and kidneys, and analyses of metallothionein (MT) and lipid peroxidation were carried out. Melatonin co-treatment brought about a significant increase in the hepatic (61%), renal (79%) and intestinal (77%) Cd concentrations as compared to those in the Cd alone group. However, the concentrations of MT in the liver and kidneys of the Cd + melatonin co-treated bank voles did not differ from those in the Cd alone group. Also, histopathological changes in the liver (infiltration of leukocytes) and kidneys (glomerular swelling and a focal tubular cell degeneration) as well as an increase (2-fold) in the renal lipid peroxidation occurred only in animals from the Cd + melatonin group. These data indicate that (1) subchronic melatonin injection has similar effect on the tissue accumulation and toxicity of Cd to that produced by a short photoperiod and (2) the Cd-induced toxicity in the liver and kidneys of melatonin co-treated bank voles is probably due to increased Cd accumulation and decreased synthesis of MT.