Grant: Project Grant - PA: Sex and Gender in Health Research (Bridge funding)

Steroid hormones are essential to life as they control many important functions in the body, including fertility, glucose metabolism, salt balance and immunity. Altered steroid hormone levels lead to many diseases, such as infertility, an impaired energy and salt balance, as well as inflammatory diseases. Cells that produce steroid hormones (steroidogenic) have developed diverse ways devoted to procuring sufficient amount of cholesterol (as per the need), which serves as an essential starting material for the biosynthesis of all steroid hormones (steroidogenesis). This arrangement helps to avoid abnormal steroid hormone production and related diseases. Despite the cholesterol-centric setup of steroidogenic cells, the potential role of cholesterol in the regulation of steroidogenesis remains unexplored. Because steroid hormones are so important for life, we speculated that steroidogenic cells must respond to a cholesterol deficiency to sustain steroidogenesis. To explore this, we used a simple approach that was not capitalized on before, and deprived steroidogenic cells to exogenous cholesterol supply, which is the major source for their steroidogenic needs. Our initial findings are very exciting, which suggest that cholesterol indeed plays a key role in the regulation of cellular events that are known to be involved in steroidogenesis. However, the mechanisms involved remain to be determined. This information is essential to improve our understanding of steroidogenesis because of its substantial clinical implications. In this research project, we will explore the mechanisms involved in the role of cholesterol in steroidogenesis in all major steroidogenic cells/tissues. We anticipate that the project outcomes will provide new insights into the molecular events involved in steroidogenesis, which in turn shine will light on future investigations in this field and open new opportunities for managing impaired steroid hormone production and related abnormalities.