哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖, 是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示, kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加, 而雌激素的这种效应是由kisspeptin神经元传导的。因此, kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化, 在非繁殖期对繁殖活动的抑制作用非常明显。此外, 甲状腺激素在繁殖期的终止上发挥着至关重要的作用, 而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖,是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示,kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加,而雌激素的这种效应是由kisspeptin神经元传导的。因此,kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化,在非繁殖期对繁殖活动的抑制作用非常明显。此外,甲状腺激素在繁殖期的终止上发挥着至关重要的作用,而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

绵羊发情周期不同组织Cry1mRNA 转录水平相对定量研究

研究表明,时钟基因Cry1在哺乳动物季节性繁殖内分泌过程中可能发挥了重要作用。文章以多浪羊(非季节性繁殖)和中国美利奴羊(季节性繁殖)为研究对象,采用实时荧光定量PCR技术对下丘脑-垂体-性腺轴主要组织Cry1在发情周期不同阶段的表达变化情况进行了跟踪检测。结果表明:绵羊Cry1在所检测组织中均有表达,其中松果体和甲状腺Cry1的表达水平较高;不同绵羊品种Cry1在发情周期不同阶段的组织表达谱基本一致,除下丘脑外,卵巢、子宫、松果体、垂体和甲状腺中Cry1的表达水平均是在发情前期达到峰值;卵巢、子宫、垂体和松果体Cry1在发情前期和发情期的表达变化幅度存在显著的品种间差异。研究结果表明:Cry1可能具有启动发情和季节性繁殖的重要作用。     

动物季节性繁殖分子调控机理研究进展

动物季节性发情繁殖涉及下丘脑-垂体-性腺轴系统复杂的神经内分泌过程,并受光照周期等环境因素的影响。褪黑激素则作为光周期信号分子调控动物季节性繁殖活动。近年来研究发现,对GnRH分泌有重要影响的Kiss1/GPR54系统既受褪黑激素的调控又受到性腺类固醇激素反馈调节,Kiss1/GPR54系统很可能是调控动物季节性繁殖的关键因子;同时动物季节性繁殖很可能还存在一条涉及TSH-DIO2/DIO3系统的逆向调控通路,该系统同样显著影响GnRH合成释放并受褪黑激素调控。文章就褪黑激素中心信号,特别是Kiss1/GPR54和TSH-DIO2/DIO3系统对繁殖季节性调控的最新研究进展进行综述。     

Kisspeptin调控动物机体代谢的研究进展

Kisspeptin是由KISS1基因编码的蛋白产物,是下丘脑GnRH上游的主要调控因子,其不仅在中枢系统调控动物的生殖,而且也可在外周局部影响动物配子发生。然而,最近诸多研究证实Kisspeptin除了在动物繁殖方面起到重要的作用外,还对动物能量平衡、摄食、肥胖以及代谢性疾病等方面起到重要的调节作用。本文就Kisspeptin在中枢神经系统和外周组织器官调控动物机体的代谢进行了详细论述,重点阐明Kisspeptin与外周代谢激素互作对动物机体代谢影响的最新进展,并总结分析了Kisspeptin在调控动物代谢方面所面临的诸多问题,以期充分理解Kisspeptin在调节动物代谢中发挥的作用,为防治动物及人类代谢紊乱性疾病提供新策略。     

RFRP-3对哺乳动物生殖功能和能量平衡的影响

哺乳动物的生殖功能受体内状态和外部环境综合作用的影响,这种综合作用通过作用于HPG轴的刺激因子和抑制因子之间的相对平衡来调控生殖。RFRP-3是目前下丘脑中唯一已知的HPG轴抑制因子。大量研究证实,RFRP-3能够抑制GnRH和LH的分泌,进而影响生殖功能。然而,RFRP-3对LH分泌的抑制作用是发生在垂体水平还是下丘脑水平尚不清楚。此外,RFRP-3还可能参与了MLT对哺乳动物季节性繁殖调控的信号通路,但是MLT对RFRP-3神经元的作用方式仍不清楚。此外,RFRP-3还可能在能量平衡和动物行为的调控中发挥着重要作用。文章就RFRP-3对HPG轴的调节机制以及其在能量平衡调节和行为调控中的作用进行了系统的阐述,并针对目前尚待解决的一些问题进行了探讨。     

雄性大熊猫褪黑素与睾酮季节性变化

褪黑素通过调控下丘脑-垂体-性腺内分泌轴使季节性繁殖动物在适宜的季节进行繁殖活动.大熊猫(Ailuropoda melanoleuca)在春季集中繁殖.为探究雄性大熊猫褪黑素和睾酮的季节性变化规律,本研究选取成都大熊猫繁育研究基地3只成年雄性大熊猫作为实验对象,在自然光照下对这3只大熊猫进行每周1次为期1年(2018年...     

不同日粮水平对初情期五指山猪性腺轴Kisspeptin/GPR54蛋白表达作用

为了阐明不同日粮水平对初情期五指山猪母猪性腺轴组织中Kisspeptin/GPR54蛋白表达作用影响,本研究采用免疫组织化学法DAB显色技术对其蛋白表达进行检测。结果表明,NRC和0.7 NRC两组实验中猪性腺轴(下丘脑,垂体,卵巢)组织中均检测到Kisspeptin和GPR54 2种蛋白的表达,并确定2种蛋白表达部位为细胞核;其中NRC组Kisspeptin蛋白下丘脑、垂体和卵巢中表达量显著比0.7 NRC组高(p0.05),2组实验中GPR54蛋白在性腺轴中表达无显著差异(p0.05),说明Kisspeptin/GPR54系统在动物初情期中的调控作用是通过个体下丘脑组织中Kiss1蛋白的表达情况得以实现的;Kisspeptin蛋白在2组实验组猪个体性腺轴中的表达规律一致,表达量从高到低排列依次为丘脑、垂体、卵巢;GPR54蛋白则在2组实验组猪个体性腺轴中表达量从高到低排列依次为卵巢、垂体、下丘脑。说明控制日粮能量的摄入并不能影响以上2种基因在猪个体性腺轴各组织中的表达规律。     

达氏鲟gpr54基因的克隆及Kisspeptin注射对其表达的影响

G蛋白偶联受体54(GPR54, G protein-coupled receptor 54)是kisspeptin (Kiss)的受体蛋白。Kisspeptin/GPR54系统通过调节促性腺激素释放激素(GnRH)的活性来参与鱼类生殖调控。为了研究Kisspeptin/GPR54系统对达氏鲟(Acipenser dabryanus)GnRH的调控功能, 克隆得到达氏鲟2个gpr54基因的全长cDNA序列, 命名为dsgpr54-1及dsgpr54-2, 分别编码379和368个氨基酸。氨基酸序列比对及进化树分析表明, 达氏鲟Gpr54与四足动物Gpr54序列一致性较高, 亲缘关系较近。荧光定量PCR研究发现, dsgpr54-1的转录本在精巢、卵巢、下丘脑、垂体、中脑及端脑等组织中均有表达, 且在下丘脑中转录水平最高; 而dsgpr54-2仅在脑组织中转录, 且在垂体、中脑及下丘脑中表达丰度均较高。为了研究Gpr54是否可以与其配体Kisspeptin结合调控下丘脑中gnrh基因的表达, 分别合成了达氏鲟Kiss-1和Kiss-2的核心十肽(10 nmol/L、1000 nmol/L), 腹腔注射到9月龄达氏鲟。结果表明, 不同浓度Kiss-1、Kiss-2注射均引起gpr54基因表达量升高, 并且10 nmol/L Kiss-2注射能够显著促进dsgpr54-2的表达(P<0.05)。另外, 不同浓度Kiss-1注射均造成了gnrh转录水平的下降; 而10 nmol/L Kiss-2注射使得gnrh1表达量上升, 而gnrh2的表达量下降, 1000 nmol/L Kiss-2注射则引起gnrh1表达量的下降, gnrh2的表达量没有显著变化。上述研究结果表明, 达氏鲟gpr54基因均能与其配体kiss-1、kiss-2相结合, 但表现出一定的受体-配体选择性差异。Kiss-1、Kiss-2通过激活Gpr54的活性, 调控下丘脑中gnrh基因的表达, 且其调控功能存在差异。     

绵羊季节性繁殖分子机制及休情季节诱导绵羊发情配种技术

季节性繁殖是限制绵羊生产效率的重要因素。季节性繁殖分子机制的深入解析是提高绵羊休情季节发情配种率的前提。研究发现,长光照与短光照条件下绵羊季节性繁殖通路中出现一系列相关信号分子变化及细胞形态学改变。基于季节性繁殖分子机制,研究者已研发出若干休情季节诱导母羊发情配种的技术或方法。本文从季节性繁殖分子机制方面总结了上述光照信号分子及垂体和下丘脑组织中细胞形态学的变化特征,及休情季节诱导母羊发情配种技术的应用效果及其利弊,并提出解决问题的关键在于寻找能够提高休情季节配种率的绿色高效的新型技术。     

Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

Most physiological and biological processes are regulated by endogenous circadian rhythms under the control of both a master clock, which acts systemically and individual cellular clocks, which act at the single cell level. The cellular clock is based on a network of core clock genes, which drive the circadian expression of non-clock genes involved in many cellular processes. Circadian deregulation of gene expression has emerged to be as important as deregulation of estrogen signaling in breast tumorigenesis. Whether there is a mutual deregulation of circadian and hormone signaling is the question that we address in this study. Here we show that, upon entrainment by serum shock, cultured human mammary epithelial cells maintain an inner circadian oscillator, with key clock genes oscillating in a circadian fashion. In the same cells, the expression of the estrogen receptor α (ERA) gene also oscillates in a circadian fashion. In contrast, ERA-positive and -negative breast cancer epithelial cells show disruption of the inner clock. Further, ERA-positive breast cancer cells do not display circadian oscillation of ERA expression. Our findings suggest that estrogen signaling could be affected not only in ERA-negative breast cancer, but also in ERA-positive breast cancer due to lack of circadian availability of ERA. Entrainment of the inner clock of breast epithelial cells, by taking into consideration the biological time component, provides a novel tool to test mechanistically whether defective circadian mechanisms can affect hormone signaling relevant to breast cancer.Key words: circadian rhythm, clock genes, estrogen receptor alpha (ERA), breast cancer cells, entrainment, serum shock     

Circadian Clock Gene Per2 Is Not Necessary for the Photoperiodic Response in Mice

In mammals, light information received by the eyes is transmitted to the pineal gland via the circadian pacemaker, i.e., the suprachiasmatic nucleus (SCN). Melatonin secreted by the pineal gland at night decodes night length and regulates seasonal physiology and behavior. Melatonin regulates the expression of the β-subunit of thyroid-stimulating hormone (TSH; Tshb) in the pars tuberalis (PT) of the pituitary gland. Long day-induced PT TSH acts on ependymal cells in the mediobasal hypothalamus to induce the expression of type 2 deiodinase (Dio2) and reduce type 3 deiodinase (Dio3) that are thyroid hormone-activating and hormone-inactivating enzymes, respectively. The long day-activated thyroid hormone T₃ regulates seasonal gonadotropin-releasing hormone secretion. It is well established that the circadian clock is involved in the regulation of photoperiodism. However, the involvement of the circadian clock gene in photoperiodism regulation remains unclear. Although mice are generally considered non-seasonal animals, it was recently demonstrated that mice are a good model for the study of photoperiodism. In the present study, therefore, we examined the effect of changing day length in Per2 deletion mutant mice that show shorter wheel-running rhythms under constant darkness followed by arhythmicity. Although the amplitude of clock gene (Per1, Cry1) expression was greatly attenuated in the SCN, the expression profile of arylalkylamine N-acetyltransferase, a rate-limiting melatonin synthesis enzyme, was unaffected in the pineal gland, and robust photoperiodic responses of the Tshb, Dio2, and Dio3 genes were observed. These results suggested that the Per2 clock gene is not necessary for the photoperiodic response in mice.     

Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

Most physiological and biological processes are regulated by endogenous circadian rhythms under the control of both a master clock, which acts systemically and individual cellular clocks, which act at the single cell level. The cellular clock is based on a network of core clock genes, which drive the circadian expression of non-clock genes involved in many cellular processes. Circadian deregulation of gene expression has emerged to be as important as deregulation of estrogen signaling in breast tumorigenesis. Whether there is a mutual deregulation of circadian and hormone signaling is the question that we address in this study. Here we show that, upon entrainment by serum shock, cultured human mammary epithelial cells maintain an inner circadian oscillator, with key clock genes oscillating in a circadian fashion. In the same cells, the expression of the estrogen receptor α (ER A) gene also oscillates in a circadian fashion. In contrast, ER A-positive and -negative breast cancer epithelial cells show disruption of the inner clock. Further, ER A-positive breast cancer cells do not display circadian oscillation of ER A expression. Our findings suggest that estrogen signaling could be affected not only in ER A-negative breast cancer, but also in ER A-positive breast cancer due to lack of circadian availability of ER A. Entrainment of the inner clock of breast epithelial cells, by taking into consideration the biological time component, provides a novel tool to test mechanistically whether defective circadian mechanisms can affect hormone signaling relevant to breast cancer.     

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

Reciprocal interactions between the host circadian clock and the microbiota are evidenced by recent literature. Interestingly, dysregulation of either the circadian clock or microbiota is associated with common human pathologies such as obesity, type 2 diabetes, or neurological disorders. However, it is unclear to what extent a perturbation of pathways regulated by both the circadian clock and microbiota is involved in the development of these disorders. It is speculated that these perturbations are associated with impaired growth hormone (GH) secretion and sexual development. The GH axis is a broadly neglected pathway and could be the main converging point for the interaction of both circadian clock and microbiota. Here, the links between the circadian clock and microbiota are reviewed. Finally, the effects of chronodisruption and dysbiosis on physiology and pathology are discussed and it is speculated whether a common deregulation of the GH pathway could mediates those effects.     

The circadian system and melatonin: lessons from rats and mice

The circadian system (CS) comprises three key components: (1) endogenous oscillators (clocks) generating a circadian rhythm; (2) input pathways entraining the circadian rhythm to the astrophysical day; and (3) output pathways distributing signals from the oscillator to the periphery. This contribution briefly reviews some general aspects of the organization of the rodent CS and pays particular attention to recent results obtained with various mouse strains, related to molecular mechanisms involved in entraining the endogenous clock and the role of the pineal hormone melatonin as a hand of the endogenous clock.