A putative mitotic checkpoint dependent on mTOR function controls cell proliferation and survival in ovarian granulosa cells.

The conserved target of rapamycin (TOR) proteins are involved in sensing nutrient levels and/or stress and the resultant control of cell growth, size, and survival. The authors assess mammalian TOR (mTOR) kinase expression in the mouse ovary and also the expression of its cofactors, Raptor, Rictor, and LST8. In granulosa cells, mTOR demonstrates high cytoplasmic/perinuclear expression. The kinase-active serine 2448-phosphorylated form of mTOR (P-mTOR) is present at very high levels during the M-phase. P-mTOR was enriched on or near the mitotic spindle and also near the contractile ring during cytokinesis. Rapamycin inhibition of mTOR resulted in both reduced granulosa cell proliferation and reduced follicle growth in vitro, each in a dose-dependent fashion. Follicles cultured in rapamycin did not undergo atresia. mTOR inhibition results in a reduction in granulosa cell proliferation, supporting a model in which stress and nutritional cues may directly influence ovarian follicle growth.