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Molecular mechanisms of FSH secretion induced by novel

新型药物诱导 FSH 分泌的分子机制

基本信息

批准号：
03454391
负责人：
IBUKI Yoshito
金额：
$ 4.22万
依托单位：
Gunma University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Previous studies reported that activin alone increased FSH receptor levels by using receptor binding assay and various hormone regulated FSH receptor mRNA levels in cultures rat granulosa cells. In this study, we examined the effect of activin A on FSH receptor mRNA in cultured rat granulosa cells using a FSH receptor cRNA probe. Northern blot analysis with cRNA of FSH receptor detected mRNA transcripts of 5.5- and 2.4-kb. Both transcripts are identical to size which have been reported previously in our in vivo studies. Our data showed that activin alone stimulated FSH receptor mRNA transcripts as well as FSH receptor levels in a concentration-dependent manner. Previous studies reported that FSH may maintain its own receptor mRNA and various growth factors as epidermal growth factor(EGF), basic fibroblast growth factor(bFGF), and insulin-like growth factor-I(IGF-I) did not alter basal levels of FSH receptor mRNA but EGF or bFGF dose-dependently attenuated the stimulatory actions of FSH on FSH receptor mRNA levels. Therefore, our results indicated that the stimulatory action of activin on the levels of the FSH receptor is closely related to the stimulatory action of activin on FSH receptor mRNA levels, and compared with other growth factors, activin may play a important role in the induction of the FSH receptor.To understand the molecular mechanism of activin action, we have cloned the rat type II activin receptor from a rat ovary cDNA library. This result revealed that the receptor intracellular domain was a serine/threonine-specific protein kinase. The results that the granulosa cells contained two predominant rat type II activin receptor mRNA transcripts (6.0 and 3.0 kilobases). Furthermore, in vivo experiments showed that the mRNA levels of activin receptor in immature rat ovary has been induced according to the maturation of follicles and even after ovulation it continued to increase.

以前的研究报道，激活素单独通过受体结合实验和各种激素调节的FSH受体mRNA水平增加培养的大鼠颗粒细胞的FSH受体水平。在本研究中，我们用FSH受体cRNA探针检测了激活素A对培养的大鼠颗粒细胞FSH受体基因表达的影响。用FSH受体的cRNA进行Northern印迹分析，检测到5.5-和2.4-kb的转录产物。这两个转录本的大小完全相同，这在我们的活体研究中已经报道过。我们的数据显示，激活素单独以浓度依赖的方式刺激FSH受体mRNA转录和FSH受体水平。已有研究表明，FSH可能维持自身的受体mRNA，多种生长因子如表皮生长因子(EGF)、碱性成纤维细胞生长因子(BFGF)和胰岛素样生长因子-I(IGF-I)不改变FSH受体mRNA的基础水平，但EGF或bFGF呈剂量依赖性地减弱FSH对FSH受体mRNA水平的刺激作用。因此，我们的结果表明激活素对FSH受体水平的刺激作用与激活素对FSH受体mRNA水平的刺激作用密切相关，与其他生长因子相比，激活素可能在FSH受体的诱导中发挥重要作用。为了了解激活素作用的分子机制，我们从大鼠卵巢的cDNA文库中克隆了大鼠II型激活素受体。这一结果表明，受体胞内结构域是丝氨酸/苏氨酸特异的蛋白激酶。结果表明，颗粒细胞含有两种主要的大鼠II型激活素受体基因转录产物(6.0kb和3.0kb)。体内实验表明，激活素受体在未成熟大鼠卵巢中的表达水平随着卵泡的成熟而被诱导，甚至在排卵后继续升高。