Prohibitin-1 plays a regulatory role in Leydig cell steroidogenesis

Mitochondria are essential for steroidogenesis. In steroidogenic cells, the initiation of steroidogenesis from cholesterol occurs on the matrix side of the inner mitochondria! membrane by the enzyme P450scc. This requires cholesterol import from the cytoplasm through the outer mitochondrial membrane, facilitated by the StAR protein. The subsequent steps leading to P450scc remain elusive. Here we report that the male transgenic mice that expressed a mutant form of a mitochondria! protein prohibitin-1 (PHB1(Tyr114Phe)) from the Fabp-4 gene promoter disr3yed smeller testes, higher testosterone, and lower gonadotropin levels compared with PHB1-expressing and wild-type mice. A subsequent analysis of the testis and Leydig cells from the mice revealed that PHB1 played a previously unknown regulatory role in Leydig cell steroidogenesis. This includes a role in coordinating cell signaling, cholesterol homeostasis, and mitochondria! biology pertaining to steroidogenesis. The implications of our finding are broad as the initial stages of steroidogenesis are indistinguishable across steroidogenic cells.

Automated summary

Mitochondria play a crucial role in steroidogenesis, particularly in cholesterol transport and P450scc enzyme synthesis. A study on transgenic mice reveals that PHB1 has a regulatory role in Leydig cell steroidogenesis, involving cell signaling, cholesterol homeostasis, and mitochondrial biology.