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Study for phathophysiology of precocious puberty

性早熟的病理生理学研究

基本信息

批准号：
07557365
负责人：
MINEGISHI Takashi
金额：
$ 1.41万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557365/
关键词：
FSH receptor precocious puberty desensitization COS細胞

项目摘要

We have examined the DNA sequences of FSH receptor cording region from the patients of precocious puberty, and we have found a point mutation in these samples. Currently we try to see the functional significance of this mutation using receptor cDNA transfected cells.Because it is well documented that the FSH receptor is internalized as a consequence of hormone binding, we examine the ability of cells expressing FSH receptor to mediate ^<125>I-FSH internalization. In this experimental approach, the cells were incubated at 37 C in the continuous presence of ^<125>I-FSH and at various times were assayd for surface-bound and internalized ^<125>I-FSH.The results indicated that a fast down-regulation of cell surface FSH receptor and a 50% loss of cell surface receptors occurred after 4 h incubation. It will be important to identify which parameters determine the rate of internalization of the hormone-occupied receptor in different cells. Since the preincubation with forskolin or FSH causes a decrease in the cAMP response to FSH,the preincubation conditions result in desensitization of the gonadotropin-responsive adenylyl cyclase. Therefore these results reveal evidence of desensitization occurring in the absence of receptor down-regulation, suggesting that uncoupling of the FSH receptor is also present in this cell types. Uncoupling of the receptor may be defined as a process by which the functional activity of the receptor is decreased despite a maintained receptor number, whereas down-regulation implies a reduction in the number of available receptors.

我们检测了性早熟患者FSH受体编码区的DNA序列，发现在这些样本中存在一个点突变。目前，我们试图用受体cDNA转染的细胞来观察这种突变的功能意义，因为有充分的证据表明FSH受体是作为激素结合的结果而内化的，所以我们检测了表达FSH受体的细胞介导^ I-FSH内化的能力<125>。在本实验方法中，细胞在37 ℃下孵育<125>，并在不同时间测定细胞表面结合和内化的β-I-FSH<125>，结果表明，细胞表面FSH受体在孵育4小时后迅速下调，细胞表面受体损失50%。重要的是要确定哪些参数决定了在不同细胞中的蛋白质占据受体的内化速率。由于与毛喉素或FSH预孵育导致cAMP对FSH的反应降低，因此预孵育条件导致促性腺激素反应性腺苷酸环化酶脱敏。因此，这些结果揭示了在没有受体下调的情况下发生脱敏的证据，表明FSH受体的解偶联也存在于这种细胞类型中。受体的解偶联可以定义为这样的过程，通过该过程，尽管维持受体数量，但受体的功能活性降低，而下调意味着可用受体数量的减少。