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。     

羊促性腺激素释放激素主动免疫去势的研究进展

促性腺激素释放激素(GnRH)是由下丘脑神经内分泌小细胞产生的十肽激素,主要通过下丘脑-垂体-性腺轴(HPG)参与调控动物的生殖活动,也可直接作用于性腺或其他器官发挥重要功能。GnRH免疫去势作为当前一种动物友好的去势方法在生产中应用和推广。本文综述了GnRH的分子结构和生物学功能、GnRH主动免疫的应用、GnRH免疫在改善公羊生产性能和繁殖性能上的研究进展,为进一步研究GnRH主动免疫在公羊繁殖中的作用提供一定理论支撑,以提高羊养殖业的经济效益和社会效益。     

GnRH—I疫苗的功能及其应用的研究进展

随着生物化学、免疫学及内分泌学的发展，出现了一个新的边缘学科——激素免疫学，并由此出现了激素免疫中和技术（Hormone immunoneutralization，HIN），即用抗体中和体内的内源性激素的生物活性。这是一种特殊的自体免疫形式，是影响内分泌调节系统的一种极为灵敏和高度特异性的方法。由此，GnRH—I疫苗开始正式提出，其作用原理是：GnRH—I疫苗主动免疫动物后，机体产生大量的抗GnRH—I的特异性抗体，     

促性腺激素释放激素及其类似物的功能与应用

促性腺激素释放激素（gonadotropin releasing hormone，GnRH）是主要由下丘脑合成的直链十肽激素，以脉冲形式分泌进入丘脑下部垂体门脉系统到达垂体前叶，或进入神经分泌轴突末端，调控垂体促卵泡激素（follicle-stimulating hormone，FSH）、促黄体素（1uteinizing hormone，LH）的合成与分泌。它是神经、免疫和内分泌调节系统相互联系的重要信号分子，与性腺和胎盘及生殖功能密切相关。     

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     

褪黑素调控动物生殖内分泌的研究进展

褪黑素(MLT)是松果体分泌的一种神经内分泌激素,具有参与免疫反应、调节生命活动的节律性等多种生物学功能,并与生殖内分泌息息相关。目前对于褪黑素的研究主要集中在人类的癌症和植物等方面,而关于动物生殖内分泌的研究较少,深度较浅。研究表明,褪黑素可以调控动物下丘脑-垂体-性腺轴生殖相关激素的内分泌作用,抑制或促进促性腺激素释放激素(GnRH)、促卵泡素(FSH)、促黄体素(LH)、性腺激素的分泌。而在不同物种间,褪黑素作用效果却不同。论文综述了褪黑素对促性腺激素释放激素、促卵泡素、促黄体素、性腺激素以及其他与生殖相关激素的调控,为褪黑素调控动物生殖内分泌的的研究提供参考,以期对褪黑素在动物生殖调控中的作用更深入了解。     

菟丝子总黄酮对生殖内分泌调节的研究进展

近年来,菟丝子在临床上经常用于治疗生殖内分泌类疾病,且作用效果显著。菟丝子是旋花科植物,具有毒副作用小、无耐药性、富含多种营养物质、成本低廉等优点,是纯天然的药用植物。菟丝子总黄酮是菟丝子中最有效的成分,具有止泻、滋补肝肾、益精壮阳和安胎等功效,不仅对雌雄动物生殖内分泌活动有调节作用,还对免疫、心脑血管等多个系统具有药理作用。动物的生殖内分泌活动主要由下丘脑-垂体-性腺轴调控,包括生殖激素的分泌以及精子的发生、卵泡的发育,对动物生殖繁育起着重要作用。绝大多数动物的生殖内分泌疾病都与下丘脑-垂体-性腺轴所调节的生殖激素以及生殖器官的发育状态有关,生殖激素可以通过直接或间接作用引起下丘脑-垂体-性腺轴功能性障碍疾病。鉴于目前经济动物禁用激素类药物,因此迫切需要研究安全有效低毒的中草药的作用及其机理,为其广泛应用奠定基础。文章介绍了菟丝子总黄酮主要的药理作用,并详细阐述了菟丝子总黄酮对下丘脑-垂体-性腺轴不同级内分泌活动的调控作用,为今后进一步研究菟丝子总黄酮对下丘脑-垂体-性腺轴调控的作用靶点和作用机理提供参考。     

家畜免疫去势研究进展

传统的手术去势技术正受到动物福利和规模化标准化畜牧生产需求的挑战,作为手术去势的优势替代方法,免疫去势能够很好地阻滞睾丸发育,控制性行为,避免手术带来的痛苦。免疫去势是采用免疫学方法破坏下丘脑-垂体-性腺轴的激素平衡,通过降低促性腺激素释放激素（GnRH）、黄体生成素（LH）和卵泡刺激素（FSH）的水平,进而使性腺激素水平降低,最终抑制性腺功能,达到去势的目的。免疫去势分为激素免疫去势和基因免疫去势,其靶标经历了下丘脑-垂体-性腺轴自下而上的筛选,依次为睾酮、LH、FSH、GnRH、吻素-1（KISS-1）,其中位于下丘脑-垂体-性腺轴上游的GnRH激素、GnRH和KISS-1基因3种靶标去势效果较好。免疫去势效果及机制的相关研究表明,免疫去势具有改善生产性能、安全和可逆的特点,但其可逆性机制还不清楚。去势导致肾上腺发挥代偿作用,但目前免疫去势的肾上腺代偿研究鲜见报道。文章首先介绍了几种靶标的免疫去势机制,其次对免疫去势的特点和应用进行了讨论,旨在为推动免疫去势技术在动物生产繁殖领域的应用提供理论依据。     

家畜免疫去势研究进展

传统的手术去势技术正受到动物福利和规模化标准化畜牧生产需求的挑战,作为手术去势的优势替代方法,免疫去势能够很好地阻滞睾丸发育,控制性行为,避免手术带来的痛苦。免疫去势是采用免疫学方法破坏下丘脑-垂体-性腺轴的激素平衡,通过降低促性腺激素释放激素(GnRH)、黄体生成素(LH)和卵泡刺激素(FSH)的水平,进而使性腺激素水平降低,最终抑制性腺功能,达到去势的目的。免疫去势分为激素免疫去势和基因免疫去势,其靶标经历了下丘脑-垂体-性腺轴自下而上的筛选,依次为睾酮、LH、FSH、GnRH、吻素-1(KISS-1),其中位于下丘脑-垂体-性腺轴上游的GnRH激素、GnRH和KISS-1基因3种靶标去势效果较好。免疫去势效果及机制的相关研究表明,免疫去势具有改善生产性能、安全和可逆的特点,但其可逆性机制还不清楚。去势导致肾上腺发挥代偿作用,但目前免疫去势的肾上腺代偿研究鲜见报道。文章首先介绍了几种靶标的免疫去势机制,其次对免疫去势的特点和应用进行了讨论,旨在为推动免疫去势技术在动物生产繁殖领域的应用提供理论依据。     

绵羊双胎苗的原理、使用方法与应用效果

1原理与作用绵羊双胎苗是生殖免疫新技术的应用,是现代高新生物工程,是目前国内外以主动免疫技术方式将性激素抗原用于绵羊,提高母羊产双羔的新举措。此项技术的基本原理是将性激素与大分子的物质偶联,形成免疫原,给绵羊注射后,使其在体内产生相应的激素抗体,主动或被动中和动物体内的性腺激素,使该激素的生物活性全部或部分丧失,从而引起内分泌平衡的改变,即减少了性激素对丘脑和垂体的负反馈,从而引起促性腺释放激素和卵胞刺激素、促黄体生成素分泌的增     

促性腺激素释放激素及其类似物在母猪繁殖中应用的研究进展

促性腺激素释放激素(gonadotropin-releasing hormone,GnRH))是下丘脑分泌的生殖激素,主要通过下丘脑-垂体-性腺轴参与调控动物的生殖活动,也可直接作用于性腺或其他器官发挥重要功能。哺乳动物的GnRH具有相同的十肽结构,通过改变十肽结构中第六、九、十位氨基酸可合成不同的GnRH类似物。GnRH及其类似物可通过刺激促黄体素(LH)分泌、抑制雌激素受体二聚化及调节胚胎附植期相关蛋白质的合成来影响动物的繁殖性能。GnRH及其类似物已被证明可提高猪的繁殖力。在母猪生产中,GnRH类似物的应用仍存在受胎次影响、促进排卵但不能增加产仔数等问题。文章主要从GnRH的来源与功能、GnRH及其类似物的结构、GnRH受体(GnRHR)的结构与功能、GnRH及其类似物对母猪繁殖性能的影响,以及存在的问题与展望五方面介绍了GnRH及其类似物在母猪繁殖中的应用研究进展。     

The effect of LH releasing hormone on testosterone levels in the blood of boars with sexual dysfunctions]

The levels were assessed of testosterone in the blood plasma before and 90 minutes after i.v. application of 1 mg of synthetic LH-releasing hormone to 57 boars with disorders of sexual functions and to 43 boars without sexual dysfunctions. The group of animals with sexual disorders included boars with inferior ejaculate quality and low fertility (24 animals) and cases with disturbed sexual potency (33 boars). In animals with the studied changes of sexual functions, compared with boars without sexual dysfunctions, no statistically significant difference was found in the basal concentration of testosterone in the blood. LH-releasing hormone application increased significantly the testosterone levels in the group of boars without sexual disorders by 99.5% on an average and in the whole group of animals with changes in sexual functions approximately by only 65.8%. At the same time in the subgroup of inferior ejaculate quality and low fertility the post-application increase of testicular incretion reached 60.4% and in potency disorders 61.6% and was statistically insignificant in the latter. On the basis of these findings it was derived that in boars with reproduction deviations there existed a decreased incretion reserve of the system hypophysis - testicle and the involvement of this factor in the formation of the studied sexual disorders is assumed. The obtained results are discussed in view of the earlier findings about the incretion reserve of the testicles in boars with changes in sexual functions.     

Pituitary receptors for GnRH and estradiol, and pituitary content of gonadotropins in beef cows. I. Changes during the estrous cycle

To further characterize the endocrinological changes in the hypothalamo-hypophyseal axis thoughout the bovine estrous cycle, cycling beef heifers (n = 24) were randomly assigned to six groups. These heifers were slaughtered 6, 12, 18, 19, 20 or 21 days following their previous estrus (day 0). Anterior pituitaries and hypothalami were collected. Hypothalami were divided into the preoptic area and medial basal hypothalamus, and content of gonadotropin-releasing hormone (GnRH) was quantified by radioimmunoassay. Contents of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the anterior pituitary gland were quantified by radioimmunoassay. Membrane receptors for GnRH were quantified by a standard curve technique and receptors for estradiol in anterior pituitary cytosol were quantified by saturation analysis. There was no significant change in content of GnRH in the hypothalamus or content of FSH in the anterior pituitary on any of the days examined; however, content of GnRH in the preoptic area was lower (P less than .1) on day 19 postestrus. Cytosolic receptors for estradiol increased (P less than .05) on day 18 post-estrus and returned to baseline by day 19. Content of LH and the number of receptors for GnRH in the anterior pituitary gland decreased (P less than .01) on day 19 postestrus, and the number of receptors for GnRH remained low through day 21 postestrus. The reduction in anterior pituitary content of LH was transient indicating that synthesis of LH restores pituitary content to preovulatory levels before the number of receptors for GnRH returns to normal.     

Effect of CD14/TLR4 antagonist on GnRH/LH secretion in ewe during central inflammation induced by intracerebroventricular administration of LPS

Background: Immune stress induced by lipopolysaccharide(LPS) influences the gonadotropin-releasing hormone(GnRH)/luteinizing hormone(LH) secretion. Presence of LPS interacting Toll-like receptor(TLR) 4 in the hypothalamus may enable the direct action of LPS on the GnRH/LH secretion. So, the aim of the study was to investigate the influence of intracerebroventricular(icv) injection of TLR4 antagonist on GnRH/LH secretion in anestrous ewes during LPS-induced central inflammation. Animals were divided into three groups icv-treated with: Ringer-Locke solution, LPS and TLR4 antagonist followed by LPS.Results: It was demonstrated that TLR4 antagonist reduced LPS-dependent suppression of GnRH gene expression in the preoptic area and in the medial basal hypothalamus, and suppression of receptor for GnRH gene expression in the anterior pituitary gland. It was also shown that TLR4 antagonist reduced suppression of LH release caused by icv injection of LPS. Central administration of LPS stimulated TLR4 gene expression in the medial basal hypothalamus.Conclusions: It was indicated that blockade of TLR4 prevents the inhibitory effect of centrally acting LPS on the GnRH/LH secretion. This suggests that some negative effects of bacterial infection on the hypothalamic-pituitary-gonadal axis activity at the hypothalamic level may be caused by central action of LPS acting through TLR4.     

Kisspeptin as a master player in the central control of reproduction in mammals: An overview of kisspeptin research in domestic animals

The hypothalamo‐pituitary‐gonadal (HPG) axis is the regulatory system for reproduction in mammals. Because secretion of gonadotropin‐releasing hormone (GnRH) into the portal vessels is the final step at which the brain controls gonadal activities, the GnRH neuronal system had been thought to be central to the HPG axis. A newly discovered neural peptide, kisspeptin, has opened a new era in reproductive neuroendocrinology. As shown in a variety of mammals, kisspeptin is a potent endogenous secretagogue of GnRH, and the kisspeptin neuronal system governs both the pulsatile GnRH secretion that drives folliculogenesis, spermatogenesis and steroidogenesis, and the GnRH surge that triggers ovulation in females. The kisspeptin neuronal system is therefore considered a master player in the central control of mammalian reproduction, and kisspeptin and related substances could therefore be valuable for the development of novel strategies for the management of fertility in farm animals. To this end, the present review aimed to summarize the current research on kisspeptin signaling with a focus on domestic animals such as sheep, goats, cattle, pigs and horses.     

Use of the gonadotropin‐releasing hormone (GnRH) stimulation test to monitor gonadal function in intact adult male cats

The gonadotropin‐releasing hormone (GnRH) stimulation test is a common procedure used to investigate normality of the pituitary‐gonadal axis in mammals. There is very little information on the technique, its efficacy and side effects in small animals and in particular no information for male cats. In dogs, such test is performed by intravenous (IV) administration. With cats, the number of times the animal needs to be restrained for blood sampling should be the least possible. The purpose of this study was to assess efficacy and side effects of the GnRH stimulation test in tomcats comparing the IV with the intramuscular (IM) route of administration. A GnRH stimulation test was performed in eight adult tomcats through IM or IV administration of 50 μg gonadorelin. The response of the pituitary‐gonadal axis was assessed by measuring serum testosterone on blood samples collected prior to and 1 hr following treatment. When considering each single group of cats, the post‐stimulation serum testosterone values were significantly higher than the pre‐treatment ones (p < .05). When comparing the two groups of cats, basal testosterone concentrations did not differ, and also post‐GnRH testosterone concentrations did not differ. In conclusion, in the cats of our study, the GnRH stimulation test produced the same results following the IM or the IV route of administration. Therefore, in tomcats, the IM route can be considered as effective as the IV one and should be preferred when doing a GnRH test.     

Influence of dose, frequency, and duration of infused gonadotropin-releasing hormone on secretion of luteinizing hormone and follicle-stimulating hormone in nutritionally anestrous beef cows.

Nutritionally induced anovulatory cows were ovariectomized and used to determine the relationships between dose, frequency, and duration of exogenous gonadotropin-releasing hormone (GnRH) pulses and amplitude, frequency, and concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum. In Experiment 1, cows were given pulses of saline (control) or 2 micrograms of GnRH infused i.v. during a 0.1-, 1.25-, 5-, 10-, or 20-min period. Concentrations of LH and FSH during 35 min after GnRH infusion were greater than in control cows (P < 0.01), and FSH concentrations were greater when GnRH infusions were for 10 min or less compared with 20 min. In Experiment 2, the effect of GnRH pulse frequency and dose on LH and FSH concentrations, pulse frequency, and pulse amplitude were determined. Exogenous GnRH (0, 2, or 4 micrograms) was infused in 5 min at frequencies of once every hour or once every 4th hr for 3 d. There was a dose of GnRH x frequency x day effect on LH and FSH concentrations (P < 0.01), indicating that gonadotropes are sensitive to changes in pulse frequency, dose, and time of exposure to GnRH. There were more LH pulses when GnRH was infused every hour, compared with an infusion every 4th hr (P < 0.04). Amplitudes of LH pulses were greater with increased GnRH dose (P < 0.05), and there was a frequency x dose x day effect on FSH pulse amplitude (P < 0.0006). We conclude that LH and FSH secretion in the bovine is differentially regulated by frequency and dose of GnRH infusions.     

In utero programming of sexually differentiated gonadotrophin releasing hormone (GnRH) secretion

It has long been recognised that steroids can have both organisational and activational effects on the reproductive neuroendocrine axis of many species, including the sheep. Specifically, if the ovine foetus is exposed to testosterone during a relatively short 'window' of in utero development (from approximately day 30-90 of a 147 day pregnancy) the neural mechanisms regulating gonadotrophin releasing hormone (GnRH) secretion become organised in a male-specific manner. In post-natal life the consequences of foetal androgen exposure are sexually differentiated responses of the GnRH neuronal network to activation by factors such as photoperiod and ovarian steroid hormones. Studies in the gonadectomized lamb have demonstrated that elevated concentrations of oestrogen (E) are unable to trigger a preovulatory-like GnRH surge in the male and the androgenized ewe lamb. Further, these animals have markedly reduced sensitivity to the inhibitory actions of progesterone on tonic GnRH release compared with normal ewes. The reasons for these abnormal steroid feedback mechanisms may reside in sexually dimorphic inputs to the GnRH neurone, including those from oestrogen-receptive neurones in the arcuate nucleus that synthetize the neuropeptide, neurokinin B (NKB). The consequences of in utero androgen exposure are reflected in a progressive and dramatic impairment of fertility in the ovary-intact ewe.