Abstract

Immunohistochemistry assays for GRP78 were performed on endometrial samples obtained from women with PCOS (n = 8) and control women subjected to hysterectomy (n = 8). Western blot analysis for GRP78 and glucose uptake was assessed in a telomerase-immortalized human endometrial stromal cell line (T-HESC) exposed to testosterone for 24 or 48 hours and challenged to an insulin short-term stimulation. Tukey test was performed for human samples comparison. Student t test or ANOVA-Bonferroni test was carried out according to the in vitro experiment. P < .05 was considered as significant. Results: GRP78 stromal immunostaining was reduced in PCOS endometria compared to controls (P < .05). The T-HESC shows a testosterone-dependent downregulation of GRP78 protein content (P < .05), concomitant with half-reduction in glucose uptake compared to controls (P < .05). Moreover, enhanced small interfering RNA against GRP78 messenger RNA leads to a decrease in glucose uptake (P < .05). Such effects were reverted by hydroxyflutamide, an inhibitor of androgen receptor. Conclusion: These results suggest that hyperandrogenemic PCOS environment could compromise the endometrial homeostasis confirmed by the decrease in glucose uptake induced by testosterone and exhibited by stromal cells.