孕酮受体介导哺乳动物雌性生殖活动的分子机理

孕酮作为一种甾体激素,在哺乳动物雌性生殖活动的调控中起着关键作用。孕酮的生理功能依赖于核孕酮受体介导的基因组效应和膜孕酮受体介导的非基因组效应,这两种效应共同介导了孕酮在各种雌性生殖活动中的不同作用,包括排卵、胚胎植入、妊娠维持、分娩启动和乳腺发育等。近年来,通过基因芯片技术筛选出大量的孕酮下游靶基因,但至今未能在这些基因的启动子区域上找到传统意义上的孕酮响应元件,故推测核孕酮受体调节下游靶基因转录活动的方式可能不同于传统的类固醇核受体。基于目前最新的研究成果,文章综述了在哺乳动物雌性生殖活动中,孕酮受体介导各种生理效应的分子机理。     

精子中孕酮的非基因组效应

孕酮是调节哺乳动物成熟精子功能最重要的生理激素,能瞬时增加精子胞内Ca2+和c AMP含量,激活精子获能、超活化、趋化性和顶体反应等生理功能。由于成熟精子基因转录沉默,孕酮的生理效应主要通过相关膜受体介导的非基因组效应实现,而探讨孕酮非基因组效应机制一直是生殖领域的研究热点。本文将从孕酮对精子生理功能的影响,精子细胞膜上可能的孕酮受体以及孕酮相关的细胞内信号通路等方面对目前研究进展进行综述。     

PGF_(2α)诱导的早期反应基因参与黄体退化的研究进展

哺乳动物卵巢黄体的存留对母畜生殖活动具有重要的作用。前列腺素F2α(PGF2α)是哺乳动物的主要溶黄体因子,通过与其受体结合,激活一系列早期反应基因,进而诱导黄体的功能性(孕酮水平下降)和结构性退化(细胞程序性死亡)。虽然PGF2α已被广泛应用于动物的同期发情、分娩控制和繁殖障碍治疗等方面,但其溶解黄体的分子机制尚未完全明确。综述了PGF2α受体及其诱导的早期反应基因参与卵巢黄体退化的研究进展,旨在为进一步研究PGF2α诱导黄体退化的分子机制提供理论依据。     

孕酮调节途径在着床过程中的作用

孕酮对于哺乳动物排卵、受精、着床、蜕膜化及妊娠维持均起到重要作用.孕酮主要通过孕酮受体(PR)起作用,PR基因敲除的小鼠表现为多种生殖障碍.此外,PR作用的发挥还需要类固醇受体辅助激活因子(SRC)和FK506结合蛋白4(Fkbp52)等辅助因子的参与.目前采用高通量基因芯片技术,筛选出许多直接或间接受孕酮调节的基因,其中同源盒基因、免疫反应基因-1、Indian hedgehog、12 / 15脂肪氧合酶、钙离子结合蛋白等在胚泡着床过程中起重要作用.本文就孕酮调节途径在胚泡着床研究方面的进展作一简要综述.     

LH/CG受体基因克隆与表达的研究进展

LH/CG受体是一种与G蛋白偶联的在哺乳动物生殖及性功能调节起重要作用的糖蛋白激素受体。介绍了鼠、猪及人等哺乳动物、鸟类、鱼类LH/CG受体基因及昆虫,无脊椎动物等LH/CG类受体的基因克隆表达及特性。     

Kisspeptins/GPR54神经内分泌系统对哺乳动物生殖活动的调控

哺乳动物的生殖活动受到神经内分泌系统的精确调控。近年来的研究表明,KISS-1基因的表达产物Kisspeptins及其G蛋白偶联受体（G protein coupled receptor 54,GPR54）在这一调控网络中发挥着重要作用,与哺乳动物青春期启动、发情排卵及季节性繁殖等过程密切相关。该文就近年来Kisspeptins/GPR54系统对哺乳动物生殖活动调控的研究进展进行简述。     

miRNA介导PGR信号通路在雌性生殖功能调节中的作用机制

MicroRNA(miRNA)作为重要的后转录调节因子参与多种生理活动。孕酮(Progesterone,P4)是重要的甾类激素,通过结合特异性受体——孕酮受体(Progesterone receptors , PGR)发挥生理作用。PGR作为核受体超家族的一员参与调控生殖相关组织或非生殖相关组织的功能。P4/PGR和miRNA可单独在雌性生殖中发挥调控作用。然而,在雌性生殖过程中,miRNA和P4/PGR的相互作用对调控排卵等雌性生殖活动起到非常重要的作用,但作用机制还未阐明。本文综述了miRNA调节P4产生、PGR基因表达以及P4/PGR调节miRNA表达的可能作用方式,为更好地研究miRNA和P4/PGR在雌性生殖中的作用提供理论基础。     

血清孕酮水平检测在克隆胚胎移植受体牛的筛选及妊娠诊断中的应用

目的:孕酮(progesterone,P4)作为一种生殖激素,在牛的发情期和妊娠期呈规律性变化,且在妊娠的建立和维持过程中发挥着重要作用。拟应用孕酮浓度测定辅助人工观察筛选克隆胚胎移植受体牛并监测其整个妊娠过程。方法:通过对自然配种牛不同生殖阶段血液中孕酮水平的分析,建立其在发情初期、妊娠期孕酮浓度的变化规律,以此为依据辅助人工观察筛选适合胚胎移植的受体牛。同时将在体外培养7天后的体细胞核移植重构囊胚移植到所筛选出的同期发情的受体牛子宫内,并应用孕酮测定监测其妊娠状态。实验结果:(1)运用孕酮检测筛选克隆胚胎移植受体牛时,当孕酮浓度在发情第0天和第5天分别为≤0.64nmol/L和2～8nmol/L时,适宜作为胚胎移植受体牛,根据此筛选指标能够排除50%左右假发情牛。(2)运用孕酮检测较传统的人工观察方法,胚胎移植的克隆牛出生率提高了7.1倍。结论:运用牛血清孕酮检测方法能有效提高母牛生理周期判断的准确性,有利于选择合适的胚胎移植受体牛,既能实时、有效地监测怀孕受体牛的妊娠状态,又避免了靠人工观察受体牛返情、流产时的人为疏漏和误判,有效地提高受体牛的利用率,提高克隆牛的生产效率,并能推广应用于畜牧行业牛的生产繁育中。     

黄体类固醇激素受体的结构功能及其生理调节

在哺乳动物中,黄体的主要功能是合成并分泌孕酮,同时还合成适量的雌二醇。孕酮不但是发情周期长短的主要调节因子,而且也为胚胎植入与发育创造合适条件。这些类固醇激素通过特异性核受体对其靶细胞发挥作用,这些受体又属于受体依赖性转录因子家族。其中,孕酮是通过其核受体亚型A或B对靶细胞发挥生理功能,而雌二醇是通过其α或β受体对靶细胞发挥生理功能。另外,这些类固醇激素还可以通过细胞膜上类固醇激素结合蛋白,迅速激活胞内信号通路发挥功能,包括孕酮膜受体组分1和2、孕酮膜受体α、β和γ,以及G蛋白偶联的雌二醇受体。该文通过阐述黄体类固醇激素受体的分子结构、生理功能及其调节机制,旨在进一步理解类固醇激素受体在黄体生理功能调节中的重要作用。     

哺乳动物同性生殖研究历程及应用前景

繁殖是所有生命形式的基础，同性生殖作为一种特殊的繁殖方式存在于自然界中。同性生殖包含孤雌生殖和孤雄生殖，在哺乳动物中尚未被发现。印记基因等表观遗传机制的存在阻碍了同性生殖胚胎发育。目前利用基因编辑已成功培育出双母系小鼠（Mus musculus domesticus）、单母小鼠和双父系小鼠，双母系小鼠和单母小鼠可正常发育并繁殖后代，双父系小鼠可存活48h。本文综述了哺乳动物同性生殖相关技术以及探究历程，总结了同性生殖技术的应用前景与发展方向。     

Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors.

Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.     

Progesterone induction of metallothionein-IIA gene expression

Expression of the metallothionein gene is known to be induced by glucocorticoids in a variety of cells. Here we show that in human cell lines containing functional progesterone receptors, the endogenous metallothionein-IIA (hMTIIA) gene is inducible by the synthetic progestins R5020 and medroxy-progesterone acetate. That this effect reflects a direct interaction with the metallothionein gene is supported by our finding that the partially purified progesterone receptor binds to the promoter region of the gene in vitro. The limits of the DNase I footprint and the guanine residues protected in methylation studies with the progesterone receptor are similar to those previously described for the glucocorticoid receptor. Thus, the hormone regulatory element of the human metallothionein-IIA gene can mediate regulation by both glucocorticoids and progestins, as does the hormone regulatory element of mouse mammary tumor virus.     

Actions of progesterone and its 5alpha-reduced metabolites on the major proteins of the myelin of the peripheral nervous system

The sciatic nerve, and the Schwann cells in particular, are able to synthesize progesterone and possess the enzymes forming the 5alpha-reduced and the 3alpha-5alpha-reduced derivatives of progesterone: dihydroprogesterone and tetrahydroprogesterone. Moreover, the progesterone receptor (PR) is present in the sciatic nerve and in Schwann cell cultures. These facts suggest that progesterone and its derivatives might play a role in the control of the synthesis of the two major proteins of the peripheral nervous system (PNS): the glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22). We have shown that: (a) dihydroprogesterone enhances the low mRNA levels of Po in the sciatic nerve of aged male rats; (b) progesterone and its derivatives stimulate the gene expression of Po in the sciatic nerve of adult rats and in Schwann cell cultures; (c) tetrahydroprogesterone increases PMP22 gene expression in the sciatic nerve of adult rats and in Schwann cell cultures. In additional experiments, utilizing agonists and antagonists of PR and GABAA receptor, we have observed that progesterone and its derivatives control Po gene expression via the PR, while tetrahydroprogesterone modulates the expression of PMP22 through the GABAA receptor.