Elucidation of mechanisms on the sex differentiation gene family and its mutual regulation

性别分化基因家族机制及其相互调控的阐明

• 批准号: 15390510
• 负责人: HOSHI Nobuhiko
• 金额: $ 10.62万
• 依托单位: Kobe University (2004-2005)Kitasato University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390510/
• 关键词: Sex differentiation; Sexual dimorphism; StAR; GnRH; hpg mouse; Apoptosis; SEP; Ad4BP; SF-1; 性的二型核; SDN-POA; AVPvN-POA; GrRH; 神経細胞; SCN; Fosファミリー; アポトーシス制御機構; Bcl-2ファミリー; Bax; 内分泌攪乱物質; 性分化; ダイオキシン(TCDD); 視床下部-下垂体-性腺系; DEHP; BPA

Gonadotropin-deficient (hpg) mice lacking GnRH caused by a deletional mutation of at least 33.5kb encompassing the distal half of GnRH and GAP have infantile reproductive systems and levels of pituitary gonadotropins that are significantly lower than normal. Although activin accelerates synthesis and secretion of FSH in vitro, it has been difficult to investigate the role of activin alone under the influence of GnRH in vivo. The present study was designed to examination whether administration of activin alone would affect gonadotropin production and gonadal development in adult hpg mice. It is clear from the present findings that inferences of activin treatment in the hpg mice under the exception of GnRH increased gonadotropin production, and activated gonadal function. SPB binds StAR protein in cells and enhances the ability of StAR protein to promote syntheses of steroid hormones. Sp1 interacts with Ad4BP/SF-1 and that Sp1 enhances Ad4BP/SF-1-DNA complex formation to regulate human StAR transcription. The hypothalamo-pituitary control of gonadotropin secretion may be affected by the smaller doses of estrogenic agents than the reproductive organs. Furthermore, the fertility rate in the male mice exposed to this estrogenic agent was closely correlated with the testosterone levels, and even more so with the rate-limiting factor of steroidogenesis, StAR gene. Morphological changes in neuronal and astroglial cells occur in the SCN with aging in a sex-specific manner with apoptosis. The sex differences in GnRH releasing function are depend on the sex differences in the activation of GnRH neurons. There is the relationship between the activation of GnRH neurons and that of the cells in AVPvN-POA. From above results, we showed a part of sex differentiation cascade with a focus on StAR gene and the differentiation of gonad, and molecular mechanism of estrogen action to the brain.

缺乏GNRH的促性腺激素缺乏症（HPG）小鼠至少33.5kb引起的GNRH引起的GNRH和GAP远端的腺体突变具有婴儿生殖系统和垂体性促性腺蛋白水平的水平，其水平明显低于正常。尽管活化素在体外加速了FSH的合成和分泌，但在GNRH在体内的影响下，很难单独研究激活素的作用。本研究旨在研究成年HPG小鼠的促性素的给药是否会影响促性腺激素的产生和性腺发育。从目前的发现可以清楚地看出，在GNRH以外，HPG小鼠中激活素治疗的推论增加了促性腺激素的产生，并激活了性腺功能。 SPB结合细胞中的星蛋白，并增强恒星蛋白促进类固醇激素的合成的能力。 SP1与AD4BP/SF-1相互作用，并且SP1增强了AD4BP/SF-1-DNA复合物的形成以调节人类恒星转录。促性腺激素分泌的下丘脑 - 垂体控制可能会受到雌激素剂量较小的雌激素的影响。此外，暴露于该雌激素剂的雄性小鼠的生育率与睾丸激素水平密切相关，甚至与类固醇生成的速率限制因子，Star Gene相关。神经元和星形胶质细胞的形态变化发生在SCN中，并以性别特异性的方式衰老。 GNRH释放功能的性别差异取决于GnRH神经元激活的性别差异。 GnRH神经元的激活与AVPVN-POA中细胞的激活之间存在关系。从上面的结果中，我们显示了性别分化级联的一部分，重点是星基因和性腺的分化以及雌激素作用对大脑的分子机制。

项目成果

Characterization of binding between SF-1 and Sp1 : Predominant interaction of SF-1 with the N-terminal region of Sp1

SF-1 和 Sp1 之间结合的表征：SF-1 与 Sp1 N 末端区域的主要相互作用

• 发表时间: 2004
• 期刊: Journal of Endocrinological Investigation 27
• 作者: Sugawara;T
• 通讯作者: T

Both N-terminal and C-terminal regions of steroid. sulphatase are important for enzyme activity.

类固醇的 N 末端和 C 末端区域。

• 发表时间: 2006
• 期刊: Journal of Endocrinology 188
• 作者: Yoshizaki T.;et al.;Sugawara T;Warita. K;Sugawara T
• 通讯作者: Sugawara T

Maternal serum markers in pregnancies associated with fetal trisomy 21 of native Japanese women with or without fetal morphological abnormalities

有或没有胎儿形态异常的日本本土女性与胎儿 21 三体性相关的妊娠母体血清标志物

• 发表时间: 2003
• 期刊: The Hokkaido Journal of Medical Science 78
• 作者: Hoshi;N
• 通讯作者: N

Kataoka S: "Cytogenetic analysis of uterine leiomyoma : the size, histopathology and GnRHa-response in relation to chromosome karyotype."European Journal of Obstetrics & Gynecology and Reproductive Biology.. 110・1. 56-62 (2003)

Kataoka S：“子宫肌瘤的细胞遗传学分析：与染色体核型相关的大小、组织病理学和 GnRHa 反应。”欧洲妇产科和生殖生物学杂志.. 110・1 (2003)。

Hoshi N: "Familial 15p tetrasomy due to extra supernumerary marker 15 chromosome associated with Robertsonian translocation between chromosomes 13 and 14."Chromosome Science. (accepted). (2004)

Hoshi N：“家族性 15p 四体性是由于额外的额外标记 15 号染色体与 13 号和 14 号染色体之间的罗伯逊易位相关。”《染色体科学》。