Expression of the glucose transporter 1 is associated with increased glucose uptake by granulosa cells during...

The preovulatory luteinizing hormone surge is known to increase glucose uptake in ovulating follicles, but the underlying mechanisms have not been explored. Members of the Slc2a family of proteins called glucose transporters mediate glucose uptake in various cell types. Our objective was to characterize the expression pattern and temporal relationship with glucose uptake of the four best-characterized glucose transporters, Slc2a1-4 in mouse ovarian granulosa cells. Analyses of mRNA levels showed that Slc2a1 was induced in granulosa cells with a peak expression at 4h after human chorionic gonadotropin (hCG) treatment. We then examined signaling cascades involved in Slc2a1 expression by pharmacological inhibitors of the ERK1/2 and mTOR pathways. Inhibition of the ERK1/2 pathway by PD0325901 reduced Slc2a1 mRNA abundance demonstrating that the ERK1/2 signaling pathway is required for Slc2a1 expression. Conversely, inhibition of the mTOR pathway with rapamycin increased the Slc2a1 transcript level, which could be attributed to the compensatory hyperactivation of ERK1/2 activity. Bioinformatic analysis followed by chromatin immunoprecipitation showed that the transcription factor Cebpb binds to the Slc2a1 promoter in hCG-stimulated granulosa cells. Finally, the glucose uptake was higher in granulosa cells collected at 4h post-hCG than those collected at 0h hCG. These results indicate that the preovulatory LH surge increases glucose uptake in granulosa cells of the ovulating follicle by inducing Slc2a1 expression through the ERK1/2 pathway and its downstream effector transcription factor Cebpb.