Steroidogenic Factor 1 and Regulation of Gonadal Formation

类固醇生成因子 1 和性腺形成的调节

• 批准号: 0723370
• 负责人: Catherine Propper
• 金额: $ 38.58万
• 依托单位: Northern Arizona University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0723370&HistoricalAwards=false
• 关键词: Steroidogenic; Factor; Regulation; Gonadal; Formation

The protein, Steroidogenic factor 1 (SF-1), impacts reproductive function. Studies of rodents and humans with SF-1 mutations demonstrate that it is necessary for appropriate formation of ovaries or testes (gonad formation). How SF-1 impacts gonad formation in non-mammalian vertebrates remains to be determined. Studies in the PI''''s lab and others indicate that exposure to a common environmental contaminant, octylphenol, alters SF-1 expression in developing gonads, possibly contributing to their altered function. Octylphenol can therefore be used as tool to test hypotheses regarding the mechanism of SF-1 activity on gonad formation. The main hypothesis of this proposal is that overproduction of SF-1 influences gonadal formation through induction of steroid hormone production in non-mammalian vertebrates. The specific objectives are to 1) determine whether increasing levels of SF-1 are correlated with changes in gonad formation and production of an important enzyme, aromatase, which is involved in synthesis of the hormone, estradiol, and 2) determine if octylphenol-induced changes in SF-1 impacts gonadal formation via hormone-based pathways. The PI will use two amphibian species: the bullfrog, a sentinel for the impact of environmental chemicals on endocrine function, and the African-clawed frog, a lab model for endocrine disruption by environmental compounds. In collaboration with a Canadian colleague the PI will determine if expression of SF-1 and aromatase is altered after exposure to octylphenol. Classic histological techniques will allow for evaluation of gonadal development in treated animals.The broader project impacts include obtaining insights into mechanisms of gonad formation in non-mammalian vertebrates. In addition, results will identify how changes in SF-1 activity may produce abnormal gonadal formation and may lead to the development of novel biomarkers for environmental disruptors of gonadal function. The PI has a history of educating graduate and undergraduate students from diverse backgrounds and of combining her research and teaching activities. She will use this proposal to continue to integrate underrepresented groups into her research program, and to allow them to form international collaborations.

这种蛋白质，类固醇生成因子1(SF-1)，影响生殖功能。对啮齿动物和带有SF-1突变的人类的研究表明，它对于卵巢或睾丸的适当形成(性腺形成)是必要的。SF-1如何影响非哺乳动物脊椎动物的性腺形成仍有待确定。S实验室和其他人的研究表明，暴露在一种常见的环境污染物辛基酚中，会改变发育中的性腺SF-1的表达，可能是导致其功能改变的原因之一。因此，辛基酚可以作为工具来检验关于SF-1活性对性腺形成的机制的假说。这一建议的主要假设是，SF-1的过度生产通过诱导非哺乳动物脊椎动物中类固醇激素的产生来影响性腺的形成。其具体目标是1)确定SF-1水平的增加是否与性腺形成和性腺形成的重要酶-芳香酶的产生相关，芳香酶参与激素雌二醇的合成，以及2)确定辛基酚诱导的SF-1的变化是否通过基于激素的途径影响性腺形成。PI将使用两种两栖动物：牛蛙，环境化学物质对内分泌功能影响的哨兵；非洲爪蛙，环境化合物扰乱内分泌的实验室模型。在与一位加拿大同事的合作下，PI将确定SF-1和芳香酶的表达在接触辛基酚后是否发生变化。经典的组织学技术将允许评估被处理动物的性腺发育。更广泛的项目影响包括获得对非哺乳动物脊椎动物性腺形成机制的洞察。此外，结果将确定SF-1活性的变化如何可能产生异常的性腺形成，并可能导致环境干扰性腺功能的新生物标记物的开发。该协会有培养来自不同背景的研究生和本科生的历史，并将她的研究和教学活动结合在一起。她将利用这一提议继续将代表性不足的群体纳入她的研究计划，并允许他们形成国际合作。