A growing body of evidence has implicated prohibitin in mitochondrial structure, function, and inheritance. Prohibitin is predominantly localized to the inner mitochondrial membrane of rat granulosa cells. Both rat and human prohibitin possesses a short transmembrane helix near their N-termini that may be integrated into the mitochondrial membranes. It has been speculated that pro-hibitin, as an inner mitochondrial membrane protein, may control ion transport and calcium-dependent ATP production. If this hypothesis is correct, then prohibitin may play a similar role in regulating the granulosa cell steroidogenic machinery, because the rate-limiting step of steroidogenesis is also located in the inner mitochondrial membrane.
The potential involvement of prohibitin in both the cell cycle and mitochondrial function is paramount to the fate of the ovarian follicle. Studies in our laboratory have demonstrated that increased prohibitin expression occurs during ovarian development. More recently, we have shown that this increased prohibitin expression correlates with granulosa cell differentiation, mitochondrial structure and function, as well as the early stages of apoptosis in an immortalized granulosa cell model.
Previously, we have shown in related studies that prohibitin expression in the ovarian tissue is age- and stage-regulated, suggesting a growth-regulatory role of prohibitin in the rat ovary. The object of the present study was to examine the spatial pattern of prohibitin during folliculo-genesis and oocyte development using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Our findings show that prohibitin is expressed in granulosa cells, theca-interstitial cells, and the oocyte in a follicular stage-dependent manner. Prohibitin expression is associated with cytodifferentiation, is upregulated by gonadotropin, and is low during cell proliferation. The intracellular localization of prohibitin is dependent on the cellular health status.