Apoptosis in rat atretic follicles is confined primarily to granulosa cells. Irrespective of the stage of follicular maturation, theca cells in all atretic follicles were TUNEL-nega-tive. Interestingly, prohibitin was highly expressed in theca cells, and its immunoreactivity progressively increased with follicular maturation. The expression of prohibitin in theca cells was much higher than that in granulosa cells. Although speculative, increased expression of prohibitin at this stage likely may be preventing theca cells from undergoing apo-ptosis.
To address this issue, we are currently utilizing a recombinant adenovirus vector to constitutively overexpressed prohibitin to determine whether this gene product has a role in delaying apoptosis. Alternatively, prohibitin may be involved in other, as-yet-unidentified physiological process, such as theca cell differentiation. Studies by Fusaro et al. demonstrated that overexpression of prohibitin in Ramos B cells blocked apoptosis induced by camptothecin, a topoisomerase-I inhibitor. This result suggests that prohi-bitin may, in part, be a cell survival or antiapoptotic factor in granulosa cells.