Direct impact of gonadotropins on glucose uptake and storage in preovulatory granulosa cells: Implications in the pathogenesis of polycystic ovary syndrome

Background Polycystic ovary syndrome (PCOS) is often associated with higher levels of LH, and arrested ovarian follicular growth. The direct impact high LH on FSH mediated metabolic responses in PCOS patients not clearly understood. Method In order to investigate the glucose metabolism preovulatory granulosa cells (GCs), we used [U14C]-2 deoxyglucose, D-[U14C]-glucose or 2-NBD analyse uptake its incorporation into glycogen. To reproduce androgenic potential patients, administered hCG both vitro vivo. role IRS-2/PI3K/Akt2 pathway was studied after knockdown specific siRNA. Immunoprecipitation assays were for assessment IRS-2, glycogen synthase protein phosphatase 1. Furthermore, examined vivo effects increase normal rat model. HEK293 co-expressing FSHR LHR demonstrate BRET change by hCG. Results human cells, more potent than stimulating uptake, however synthesis significantly upregulated only through activity via pathway. On contrary, an impaired FSH-stimulated PCOS-patients indicated a selective defect activation. Further, immature model, such that it inhibited FSH-mediated as well inhibition IRS-2 expression. These findings further validated overexpressing Flag-LHR HA-FSHR, where uptake. Notably, increased observed expressing FSHR-Rluc8 LHR-Venus possibly suggesting heteromerization presence comparison alone. Conclusion Our confirm attenuation activation level leading pathway, resulting depleted stores growth arrest patients.