Paracrine regulation of reproductive system by TGFbeta superfamily

近年来，越来越多的证据表明，转化生长因子- (TGF) β超家族生长因子在各种组织的分化、细胞增殖或功能表达中发挥着不可或缺的作用。本课题主要研究tgfβ超家族生长因子及其相关肽在生殖系统中的生理作用。结果表明：1)激活素在小鼠胚胎早期释放“2细胞阻滞”，促进胚胎发育。免疫组织化学分析和原位杂交技术检测mRNA显示，激活素在胚胎和输卵管中均有合成。激活素受体mRNA在胚胎中检测到，而在输卵管细胞中未检测到。这些结果表明，激活素是一种促进胚胎发育的自分泌因子，输卵管细胞通过提供额外的激活素来促进胚胎的生长。2)进一步探讨了激活素对垂体后叶促性腺激素分泌细胞的调节作用模式。激活素特异性地增加了促卵泡激素分泌细胞的数量。此外，还发现垂体卵泡星状细胞分泌卵泡抑素，该肽通过抑制激活素的生物活性来调节其旁分泌/自分泌作用。3) tgf β是巨噬细胞介导催乳素作用的旁分泌因子，维持大鼠黄体黄体酮分泌。我们还成功分离并鉴定了20 α -羟基类固醇脱氢酶（20 α -羟基类固醇脱氢酶）的cDNA，该蛋白是卵巢中受tgf β调控表达的靶蛋白之一。4)我们成功生产了活化素/抑制素β aa和β ab亚基、抑制素α亚基和卵泡蛋白的特异性抗体。利用这些抗体建立了这些生物活性多肽的免疫测定系统。5)成功分离马活化素/抑制素β a亚基cDNA克隆。马β - ab或α亚基，卵泡抑素的克隆也正在进行中。少

Recently, the evidence has been accumulated that transforming growth factor- (TGF) beta superfamily growth factors play indispensable roles for differentiation, cell proliferation or expression of the function of various tissues. In this research project, we focused on the physiological roles of TGFbeta superfamily growth factors and related peptides in reproductive system. The summary of the results are as follows :1) We found that activin release "2-cell block" during early embryogenesis and enhance embtyo development in mice. Immunohistochemical analysis and in situ hybridization technique to detect mRNA revealed that activin is synthesized both in the embryo and the oviduct. Activin receptor mRNA was detected in embryos but not in oviductal cells. These results suggest that activin is an autocrine factor to promote embryo development and oviductal cells help its growth by supplying additional activin.2) The mode of action of activin to regulate gonadotropin-secreting-cells in the p … More ituitary was investigated. Activin increased the number of follicle stimulating hormone secreting-cells specifically. Furthermore, it was found that folliculo-stelate cells in the pituitary secrete follistatin and this peptide regulate activin's paracrine/autocrine action by inhibiting its bioactivity.3) TGFbeta was found to be a paracrine factor from macrophage to mediate prolactin action maintaining luteal progesterone secretion in rats. We also succeeded in isolating and characterizing the cDNA of 20alpha-hydroxysteroid dehydrogenase, which is one of the target proteins which expression are regulated by TGFbeta in the ovary.4) We succeeded in producing specific antibodies to activin/inhibin betaA and betaB subunits, inhibin alpha subunits, and follistain. Using these antibodies we established immunoassay system for these bioactive polypeptides.5) We Succeeded in isolating cDNA clone of equine avtivin/inhibin betaA subunit. Cloning of equine betaB or alpha subunits, follistatin is also now under way. Less