2001 Fiscal Year Final Research Report Summary
Estimation of effects of endocrine disruptor
| Project/Area Number |
11557078
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Endocrinology
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| Research Institution | Okazaki National Research Institutes |
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Principal Investigator |
MOROHASHI Ken-ichirou National Institute for Basic Biology Professor, 基礎生物学研究所, 教授 (30183114)
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| Co-Investigator(Kenkyū-buntansha) |
佐神 文郎 エーザイ株式会社, 安全性研究所, 部長
ISHIHARA Satoru National Institute for Basic Biology Assistant, 基礎生物学研究所, 助手 (00300723)
BUNROU Sagami Eisi Co,Ltd.Drug Safety & Disposition Research Laboratories
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| Project Period (FY) |
1999 – 2001
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| Keywords | gonad / sex determination / transcription factor / Ad4BP / SF-1 |
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| Research Abstract |
It has been suspected that endocrine disruptors affect gonad sex differentiation. However, the effects has been unclear probably because lacking our understanding the molecular mechanism underlying gonad sex differentiation. Thus, in ' the present study we focused on understanding the molecular mechanism through functions of transcription factors expressed in the differentiating gonads. Sexes are determined by composition of sex chromosomes, which is occurred at fertilization. Thereafter, sexually indifferent gonads differentiate into testis or ovary according to the sex.' chromosomes. Sex hormones synthesized and secreted from the gonads are known to play pivotal roles for sex differentiation of whole body. Thus, when considering sex differentiation of all animal species, it is well accepted that the key step for sex differentiation is the gonad sex determination. Thus, we have studied the molecular mechanism underlying the gonad differentiation by focussing on molecules interacting with Ad4BP/SF-l which is essential for gonad differentiation. Through yeast two hybrid screening, a number of molecules have been isolated, some of which.encode transcription factors and other of which encode factors implicated in signal trahsduction through cell growth factors. One of the transcription factors has a paired homeo domain, and the functional significance was clearly revealed by investigating the gene disrupted mouse and by finding a human disease caused by the gene mutation. As a molcule for signal transduction, p-catenin was isolated. Functional analysis indicated that β-catenin activated Ad4BP/SF-l mediated transcription through a direct interaction. These findings help us to understand the molecular mechanisms underlying gonad sex differentiation
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