Project 418669

Steroid hormones are essential to life. They regulate critical phases of development, such as puberty, and are essential for a number of key physiological functions in our body. Inadequate levels of steroid hormones are associated with a variety of diseases including infertility, hormone-dependent cancers (prostate, breast, ovarian), osteoporosis, and autoimmune and inflammatory diseases. Thus, steroid hormone synthesis (steroidogenesis) in different steroidogenic tissues, such as adrenal glands, ovary, and testis, is finely regulated to ensure adequate amount are produced but also to avoid conditions of hormone insufficiency or excess. The fundamental framework of steroidogenesis across major steroidogenic tissues is very similar. For example, cholesterol is the common starting material for all steroid hormones. Moreover, its transport to mitochondria (a cell compartment where steroidogenesis begins) within different steroidogenic cells and subsequent utilization for the initiation of steroidogenesis, including the male sex steroid hormone (testosterone) production by the testis, is similar. However, our understanding of this essential step of steroidogenesis remains unknown. Unraveling this may open new therapeutic opportunities for a wide variety of diseases that involved impaired steroidogenesis. Recently, my team has found that a protein called prohibitin, plays an important role in testosterone production, including the functional coupling of the crucial steps across mitochondrial membrane for the initiation of steroidogenesis. However, the mechanisms involved remain to be determined, which is the focus of this international collaborative research project. Research outcomes will advance our understanding of testosterone production by the testis, particularly the role that prohibitin plays, which is entirely unknown. The knowledge gained may create new opportunities to treat testosterone deficiency and related comorbidities.