Steroidogenic Factor 1 and Regulation of Gonadal Formation

点击翻译按钮获取中文摘要

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.