Steroidogenic Factor 1 and Regulation of Gonadal Formation

这种蛋白质，类固醇生成因子1 (SF-1)，影响生殖功能。对具有SF-1突变的啮齿动物和人类的研究表明，它是卵巢或睾丸（性腺形成）适当形成所必需的。SF-1如何影响非哺乳脊椎动物性腺的形成仍有待确定。PI''‘’实验室和其他研究表明，暴露在一种常见的环境污染物辛基酚中，会改变发育性腺中SF-1的表达，可能导致性腺功能改变。因此，辛基酚可以作为工具来检验关于SF-1活性对性腺形成机制的假设。该建议的主要假设是，在非哺乳动物脊椎动物中，SF-1的过量产生通过诱导类固醇激素的产生来影响性腺的形成。具体目标是：1)确定SF-1水平的升高是否与性腺形成和一种重要酶——芳香化酶的产生相关，芳香化酶参与激素雌二醇的合成；2)确定辛基酚诱导的SF-1变化是否通过激素途径影响性腺形成。PI将使用两种两栖动物：牛蛙和非洲爪蛙，前者是环境化学物质对内分泌功能影响的哨兵，后者是环境化合物对内分泌干扰的实验室模型。在与加拿大同事的合作中，PI将确定暴露于辛基酚后SF-1和芳香化酶的表达是否发生改变。经典的组织学技术将允许评估治疗动物的性腺发育。更广泛的项目影响包括获得非哺乳动物脊椎动物性腺形成机制的见解。此外，研究结果将确定SF-1活性的变化如何导致性腺形成异常，并可能导致性腺功能环境干扰物的新生物标志物的开发。PI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起来。她将利用这一提案继续将代表性不足的群体纳入她的研究项目，并允许他们形成国际合作。

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.