Sox transcription factors: Regulatory mechanisms and impact on steroidogenesis

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Members of the Sox family of transcription factors, Sry and Sox9, are known to play important roles in sex determination and differentiation in mammals. More than 20 members of this family have been characterized, of which several are expressed in the testis. To ensure their specificity of action, Sox proteins rely on recruitment of partners and post-translational modifications. However, their role in transcriptional regulation of steroidogenesis has never been investigated. Interestingly, putative binding sites for Sox members are present in the promoters of several steroidogenic genes. Thus, Sox family members might play a crucial role in transcriptional regulation of steroidogenesis in Leydig cells. These cells supply testosterone important to maintain fertility in male and to avoid andropause related symptoms associated to aging. Steroidogenesis can be regulated at different levels such as gonads (for steroidogenic genes), pituitary (by regulating LH and FSH productions) and hypothalamus (by regulating GnRH production). Therefore, the main goal of my research program is to define the role of Sox members in functional regulation of the Hypothalamic-Pituitary-Gonadal axis, important for sex steroids production. The current proposal aims to identify which Sox members are expressed in rodent male gonads, which genes they regulate and what mechanisms regulate their activities. Overall, different approaches of molecular and cell biology will be used to better understand the role of Sox transcription factors in Leydig cells' function. As in other tissues, Sox members might be functionally redundant in steroidogenic cells, explaining the lack of steroidogenic phenotypes in Sox-deficient mice models. Results from this proposal will have a great significance for basic physiology and endocrinology of gonadal steroidogenesis in vertebrates and might be relevant for novel male contraception. In addition, our results will contribute to a better understanding of prostate cancer development and progression.