GnIH/GnRH对鸟类排卵的调控作用

鸟类卵泡的发育受下丘脑-垂体-性腺(Hypothalamic-pituitary-gonadal,HPG)轴调控,其中,下丘脑是调控各器官活动的中枢,促性腺激素抑制激素(Gonadotropin-inhibitoryhoromne,Gn IH)和促性腺激素释放激素(Gonadotropin-releasing hormone,GnRH)是下丘脑中分泌的两种神经肽,GnRH可以促进垂体中促性腺激素的释放,而Gn IH则起着与其相反的作用,GnIH/GnRH激素在鸟类的排卵调控中起着重要作用。文章对GnIH/GnRH激素的发现、分布、结构、受体以及调控等方面进行了初步探讨。     

山羊促性腺激素释放激素1基因外显子克隆及序列分析

促性腺激素释放激素1(gonadotropin-releasing hormone 1,GnRH1)是GnRH存在于脑下垂体的主要形式,它在调节生殖内分泌系统产生促性腺激素方面起着主要作用。根据牛GnRH1基因全序列设计3对引物,采用PCR-SSCP技术检测GnRH1基因外显子2、3和4在高繁殖力山羊品种（济宁青山羊）、中等繁殖力山羊品种（波尔山羊）和低繁殖力山羊品种（内蒙古绒山羊和安哥拉山羊）中的单核苷酸多态性,分析该基因对山羊高繁殖力的影响;并对山羊GnRH1基因3个外显子进行克隆测序,推导出编码的氨基酸序列,然后将山羊核苷酸和氨基酸序列与牛、人、狗、黑猩猩、猴、大鼠和小鼠7个物种的序列进行同源性比较。结果表明,在4个山羊品种中均未检测到GnRH1基因3个外显子的多态性;8个物种的核苷酸和氨基酸序列的同源性分别为73.6%～99.3%和62.0%～97.8%。可见,哺乳动物GnRH1基因外显子2、3和4序列保守性较强,该区域可能不是影响山羊高繁殖力的功能结构域。     

Kisspeptin对哺乳动物生殖调控的研究进展

Kisspeptin是由KISS1基因编码的一种神经肽。Kisspeptin与其受体是GnRH神经元上游的关键调节因子,通过调控GnRH释放刺激垂体促性腺激素的分泌。Kisspeptin在哺乳动物下丘脑、垂体和性腺等器官组织中表达,参与下丘脑-垂体-性腺(HPG)轴功能调控,在哺乳动物生殖过程中发挥重要作用。文章主要从下丘脑、垂体和性腺三个方面阐述Kisspeptin对哺乳动物生殖功能的调控作用,并就Kisspeptin在动物初情期启动、季节性繁殖和繁殖性能上的研究进行分析总结,以期为Kisspeptin在动物繁殖领域的研究和应用提供参考依据。     

生殖机能的环境调节——生殖神经内分泌学机理

一、前言生殖机能受下丘脑—垂体—性腺(H—P—G)轴这神经内分泌系统的控制。由下丘脑产生并释放到垂体门脉系统的促性腺激素释放激素(GnRH或LHRH)促进垂体分泌促性腺激素(GTH),进而控制性腺活动。性腺分泌的性激素又反过来影响下丘脑和垂体功能,也就是说性腺激素通过正、负反馈调节     

动物初情期调控的研究进展

雌性动物第一次出现发情表现并排卵的时期,称为初情期.当动物到达初情期年龄时,GnRH脉冲释放增加,GnRH能够刺激垂体释放LH和FSH,这两种激素是产生成熟配子和性腺类固醇激素分泌所必需的物质.下面就动物的初情期发生机制及调控初情期的途径和方法做以下介绍.     

关于动物下丘脑部激素的介绍

1促性腺激素释放激素促性腺激素释放激素(GnRH),由下丘脑内侧视前区,下丘脑前部,弓状核和视交叉上核的神经核团分泌。哺乳动物下丘脑分泌的GnRH均为由9种氨基酸组成的直链式十肽,禽类、两栖类和鱼类的分子结构与哺乳类略有差异。下丘脑与垂体间没有直接的神经支配,而是通     

哺乳动物下丘脑-垂体-卵巢轴的研究进展

哺乳动物的下丘脑、垂体和卵巢分泌的激素在功能上相互作用,构成一个完整的神经内分泌生殖调节体系,即下丘脑垂体卵巢轴,它在生殖活动中起着主要的调节作用。下丘脑中分布的GnRH神经元可以分泌GnRH,GnRH调节垂体中促性腺激素细胞分泌促性腺激素FSH和LH,促性腺激素作用于卵巢受体,引起雌激素和孕酮分泌并影响生殖活动。从组织学角度上研究,下丘脑垂体卵巢轴中的结构,如GnRH神经元、促性腺激素细胞、卵泡随周期性变化而呈现出不同的形态结构和分泌特点。因此,对以上各种细胞的研究是探讨其所分泌激素的基础,而下丘脑垂体卵巢轴中的各种激素的研究则是了解和控制动物繁殖机能的关键。     

哺乳动物性晚熟5个相关基因的研究进展

越来越多的基因突变对哺乳动物性发育有影响。在造成青春期异常的原因中,约75%是由于基因突变造成的。作者简要介绍了DAX1、KAL1、FGFR1、PROP1、PROKR2/ PROK2基因突变与哺乳动物性晚熟的关系。     

Kisspeptins/GPR54系统及其在动物性发育中的作用

促性腺释放激素（gonadotropin-releasing hormone,GnRH）脉冲式释放的激活是动物性发育的关键。研究结果发现,kisspeptins/GPR54系统对GnRH脉冲式释放的激活起到了重要作用,是性发育启动的调节器。在kisspeptins/GPR54胞内信号通路方面的研究也已经证实,kisspeptins能通过GPR54受体激活多种信号,以发挥其它功能。另外,光周期、机体能量储备等也是影响动物性发育的重要因素。     

促性腺激素释放激素在牦牛睾丸中的免疫组化定位

牦牛属于季节性繁殖牛科动物,且生长在海拔较高的寒冷地带。促性腺激素释放激素(GnRH)可通过下丘脑-垂体-性腺轴作用于性腺,调节性腺发育及生殖功能。为探讨GnRH在牦牛睾丸中的作用机理,本文对牦牛睾丸进行免疫组化SP法染色,研究GnRH在牦牛睾丸不同细胞中的表达特征。结果显示GnRH主要分布于睾丸组织的间质细胞与生精细胞的胞质中,且在生精细胞中呈强表达,间质细胞次之。说明GnRH对睾丸的生殖功能紧密相连,一方面通过性腺轴促进睾酮和精子的生成,另一方面通过旁分泌或自分泌的方式调节生殖激素。     

Successful use of a gonadotropin-releasing hormone (GnRH) analog for the treatment of tertiary hypogonadism (GnRH deficiency) in a 5-year-old Belgian Blue bull

A bull was referred for a progressive oligoasthenotheratozoospermia that resulted in a unsuitable seminal quality for the cryopreservation. Breeding soundness evaluation results suggested gonadal dysfunction. Because of the lack of normal ranges for these hormones in the bull, in this study, the hypogonadism and the site of the dysfunction (hypothalamus) were diagnosed by the gonadotropin-releasing hormone (GnRH) stimulation test. The evaluation of pituitary and testicular responsiveness by a GnRH stimulating test revealed a responsiveness of the pituitary and testis, thus a secondary hypogonadism (hypothalamic hypogonadism) was postulated and a therapeutic approach based on the subcutaneous administration of GnRH analog was attempted. An increase in semen volume, concentration and sperm characteristics were detected 9 weeks after the start of the treatment, corroborating the hypothalamic origin of the disease and the useful of the GnRH therapy.     

初情期启动过程中小尾寒羊下丘脑GnRH基因甲基化状态及表达量关系研究

初情期启动的早晚关系到雌性动物的繁殖性能,GnRH是动物初情期启动过程中的关键基因,其启动子区甲基化状态与GnRH mRNA表达量之间的关系尚不清楚。本研究选择初情期前、临近初情期和初情期雌性小尾寒羊的下丘脑作为样本,利用亚硫酸氢盐测序(BSP)技术和实时荧光定量PCR(qRT-PCR)技术检测了初情期不同阶段小尾寒羊GnRH启动子区的甲基化状态和GnRH mRNA的表达量,并分析二者之间的关系。结果表明:小尾寒羊到达初情期时,GnRH基因启动子区甲基化水平显著降低(P0.05),尤其是在启动子区-570位点降低最明显,而随着初情期的启动GnRH mRNA表达量呈上升趋势。结果提示,初情期启动过程中,GnRH mRNA表达量升高可能与下丘脑GnRH基因启动子区特定位点甲基化水平降低存在一定的关系。     

Pituitary responsiveness to GnRH, hypothalamic content of GnRH and pituitary LH and FSH concentrations immediately preceding puberty in gilts

To determine whether pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) or hypothalamic content of gonadotropin releasing hormone (GnRH) change before puberty, 40 prepubertal gilts averaging 7 mo of age were slaughtered before or on the second, third or fourth day after relocation and boar exposure. Some gilts responded to relocation and boar exposure as indicated by swollen vulvae, turgid uteri and enlarged ovarian follicles at the time of slaughter. Pituitary concentrations of LH and FSH and hypothalamic content of GnRH were similar between gilts that responded to relocation and boar exposure and gilts that did not respond. In addition, boar exposure and relocation had no effect on pituitary concentrations of LH and FSH or on hypothalamic content of GnRH. To determine whether pituitary responsiveness to GnRH changes before puberty, a third experiment was conducted in which 72 gilts were injected with 400 micrograms of GnRH either before or on the second, third or fourth day after relocation and boar exposure. In gilts that subsequently responded (i.e., ovulated) as a result of relocation and boar exposure, pituitary responsiveness to GnRH was reduced as compared with gilts that failed to ovulate after relocation and boar exposure. Peak concentrations of serum LH after GnRH injection were 4.6 +/- 1.3 vs 9.8 +/- .8 ng/ml for responders vs nonresponders. Peak serum FSH after GnRH injection was also lower for responders than for nonresponders (29.5 +/- 4.2 vs 41.2 +/- 2.4 ng/ml). When compared with controls, relocation and boar exposure did not significantly affect GnRH-induced release of LH and FSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic Peripheral Administration of Kappa-Opioid Receptor Antagonist Advances Puberty Onset Associated with Acceleration of Pulsatile Luteinizing Hormone Secretion in Female Rats

Puberty in mammals is timed by an increase in gonadotropin-releasing hormone (GnRH) secretion. Previous studies have shown involvement of the two neuropeptides, kisspeptin and neurokinin B (NKB), in controlling puberty onset. Little is known about the role of the other key neuropeptide, dynorphin, in controlling puberty onset, although these three neuropeptides colocalize in the arcuate kisspeptin neurons. The arcuate kisspeptin neuron, which is also referred to as the KNDy neuron, has recently been considered to play a role as an intrinsic source of the GnRH pulse generator. The present study aimed to determine if attenuation of inhibitory dynorphin-kappa-opioid receptor (KOR) signaling triggers the initiation of puberty in normal developing female rats. The present study also determined if stimulatory NKB-neurokinin 3 receptor (NK3R) signaling advances puberty onset. Female Wistar-Imamichi rats were weaned and intraperitoneally implanted with osmotic minipumps filled with nor-binaltorphimine (nor-BNI), a KOR antagonist, or senktide, a NK3R agonist, at 20 days of age. Fourteen days of intraperitoneal infusion of nor-BNI or senktide advanced puberty onset, manifested as vaginal opening and the first vaginal estrus in female rats. Frequent blood sampling showed that nor-BNI significantly increased luteinizing hormone (LH) pulse frequency at 29 days of age compared with vehicle-treated controls. Senktide tended to increase this frequency, but its effect was not statistically significant. The present results suggest that the inhibitory input of dynorphin-KOR signaling plays a role in the prepubertal restraint of GnRH/LH secretion in normal developing female rats and that attenuation of dynorphin-KOR signaling and increase in NKB-NK3R signaling trigger the onset of puberty in female rats.     

动物性成熟启动的调控机理

 人类的性早熟表现为病理状态,而在动物上,性早熟则是一个在生产上具有重要价值的经济性状。动物性成熟启动是一个复杂的生物学过程,受下丘脑-垂体-性腺轴调控。"允许信号"和"发育时钟"传达了机体生长发育、能量平衡和环境变化信息,决定了性成熟启动前期处于休眠状态的GnRH神经元激活;GnRH神经元抑制性输入减少和兴奋性输入增加引发了高频GnRH脉冲分泌,促进配子形成和性类固醇激素分泌;类固醇激素又通过负反馈通路影响GnRH分泌并促进性行为。神经胶质细胞也参与了性成熟的启动,主要涉及生长因子家族、神经细胞粘合分子和神经接触蛋白。GnRH基因的表观遗传修饰变化可能在动物性成熟启动过程中发挥了重要作用。     

Regulatory roles of leptin in reproduction and metabolism: a comparative review

Leptin plays an important role in signaling nutritional status to the central reproductive axis of mammals and appears to be at least a permissive factor in the initiation of puberty. The expression and secretion of leptin are correlated with body fat mass and are acutely affected by changes in feed intake. Moreover, circulating leptin increases during pubertal development in rodents, human females and heifers. Effects of leptin are mediated mainly via receptor activation of the JAK-STAT pathway; however, activation of alternative pathways, such as MAP kinase, has also been reported. Although the leptin receptor (LR) has not been found on GnRH neurons, leptin stimulates the release of GnRH from rat and porcine hypothalamic explants. Moreover, leptin increases the release of LH in rats and from adenohypophyseal explants and/or cells from full-fed rats and pigs. In contrast, stimulation of the hypothalamic-gonadotropic axis by leptin in cattle and sheep is observed predominantly in animals and tissues pre-exposed to profound negative energy balance. For example, leptin prevents fasting-mediated reductions in the frequency of LH pulses in peripubertal heifers, augments the magnitude of LH and GnRH pulses in fasted cows, and enhances basal secretion of LH in vivo and from adenohypophyseal explants of fasted cows. However, leptin is incapable of accelerating the frequency of LH pulses in prepubertal heifers, regardless of nutrient status, and has no effect on the secretion of GnRH and LH in full-fed cattle or hypothalamic/hypophyseal explants derived thereof. Similar to results obtained with LH, basal secretion of GH from anterior pituitary explants of fasted, but not normal-fed cows, was potentiated acutely by low, but not high, doses of leptin. Mechanisms through which undernutrition hypersensitize the hypothalamic-gonadotropic axis to leptin may involve up-regulation of the LR. However, an increase in LR mRNA expression is not a requisite feature of heightened adenohypophyseal responses in fasted cattle. To date, leptin has not been successful for inducing puberty in ruminants. Future therapeutic uses for recombinant leptin that exploit states of nutritional hypersensitization, and identification of genetic markers for genotypic variation in leptin resistance, are currently under investigation.     

GnRH依赖型性早熟遗传调控系统研究进展

性早熟在人类上表现为病理状态,而在家禽生产上则是一个具有重要经济价值的性状。人类性早熟调控机理的研究较为透彻,尤其是近年来全基因关联分析方法的应用,使得研究者对于性成熟启动相关新基因发掘及其调控网络的认识更加深入。论文综述了人类Gn-RH依赖型性早熟(GDPP)的5个基因调控系统,包括kisspeptin系统、γ-GABA系统、NPY和leptin系统、LIN28B系统和NKB系统的研究进展,为禽类早熟性状研究提供依据。     

Induction of ovulation in the prepuberal gilt by pulsatile administration of gonadotropin releasing hormone

An attempt was made to induce precocious puberty in gilts approximately 164 days of age by stimulating a luteinizing hormone (LH) secretory pattern similar to that which occurs before normal onset of puberty. Hourly iv administration of 1 μg synthetic gonadotropin releasing hormone (GnRH) for 7 or 8 days resulted in a mean serum LH concentration of 1.7 ± .3 ng/ml in three treated gilts compared with .9 ± .1 ng/ml in three control gilts (P<.08). Serum LH peak frequency was also greater (P<.05) in treated (3.4 ± .5 peaks/4 hr) than in control gilts (1.2 ± .1 peaks/4 hr), but serum LH peak amplitude was not altered (P>.33) by GnRH treatment. All treated gilts displayed estrus and ovulated within 6 days after treatment began, and all control gilts remained prepuberal throughout the study (P=.05). Only one of the three treated gilts displayed a normal estrous cycle and reovulated after treatment. Precocious ovulation but not puberty was induced in gilts by hourly administration of 1 μg synthetic GnRH, indicating that the pituitary and ovaries of 164-day-old gilts are competent and that final sexual maturation occurs at the hypothalamic level.