1996 Fiscal Year Final Research Report Summary
Study for phathophysiology of precocious puberty
| Project/Area Number |
07557365
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Gunma University |
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Principal Investigator |
MINEGISHI Takashi Gunma University School of Medicine・Dept of OB/GYN・Assistant Professor, 医学部・産科婦人科学, 講師 (00209842)
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| Co-Investigator(Kenkyū-buntansha) |
IBUKI Yoshito Gunma University School of Medicine・Dept of OB/GYN・Professor, 医学部, 教授 (40008256)
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| Project Period (FY) |
1995 – 1996
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| Keywords | FSH receptor / precocious puberty / desensitization |
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| Research Abstract |
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.
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