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.

促性腺激素缺乏 (hpg) 小鼠由于包含 GnRH 和 GAP 远端一半的至少 33.5kb 缺失突变而缺乏 GnRH，其婴儿生殖系统和垂体促性腺激素水平显着低于正常水平。虽然激活素在体外加速FSH的合成和分泌，但在体内GnRH影响下单独研究激活素的作用一直很困难。本研究旨在检查单独施用激活素是否会影响成年 HPG 小鼠的促性腺激素产生和性腺发育。从目前的研究结果可以清楚地看出，在 GnRH 除外的情况下，对 HPG 小鼠进行激活素治疗会增加促性腺激素的产生，并激活性腺功能。 SPB与细胞内的StAR蛋白结合，增强StAR蛋白促进类固醇激素合成的能力。 Sp1 与 Ad4BP/SF-1 相互作用，并且 Sp1 增强 Ad4BP/SF-1-DNA 复合物的形成，从而调节人类 StAR 转录。与生殖器官相比，下丘脑-垂体对促性腺激素分泌的控制可能受到较小剂量的雌激素药物的影响。此外，接触这种雌激素药物的雄性小鼠的生育率与睾酮水平密切相关，与类固醇生成的限速因素StAR基因密切相关。随着年龄的增长，SCN 中的神经元和星形胶质细胞会发生形态学变化，并以性别特异性的方式发生凋亡。 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中细胞的激活存在相关性。从以上结果中，我们展示了性别分化级联的一部分，重点是StAR基因和性腺的分化，以及雌激素对大脑作用的分子机制。

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)。

Sugawara T: "The potential function of steroid sulfatase activity in steroid production and steroidogenic acute regulatory protein expression."Biochem J. (In print). (2004)

Sukawara T：“类固醇硫酸酯酶活性在类固醇生成和类固醇生成急性调节蛋白表达中的潜在功能。”Biochem J.（印刷中）。