Ligand-activated peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor, dimerises with retinoid X receptor(RXR) and acts as a transcription factor translating nutritional, pharmacological and metabolic stimuli into changes in gene expression. PPARgamma is thought to serve several roles in adipocyte differentiation, fatty acid and lipid metabolism, insulin sensitivity and ovarian steroidogenesis. PPARgamma has also been shown to increase glucose uptake and metabolism in liver, adipose tissue and muscle. Thiazolidinediones(TZD), high affinity PPARgamma agonists, have been shown to improve insulin sensitivity and are used for treatment of type II diabetes. Patients with polycystic ovary syndrome(PCOS) show improvement in insulin sensitivity and a decrease in androgen production when treated with troglitazone, a PPARgamma ligand. The aim of this study was to investigate the effect of PPARgamma and RXR ligands on glucose uptake and lactate accumulation in a human granulosa cell line (HGC-5). After a 24h or 48h pre-incubation with serum, PPARgamma and RXR ligands were added to HGL-5 cells for a further 24h or 48h. The COBAS-BIO auto-analyser was used to measure glucose depletion and lactate accumulation of HGL-5s after 24h and 48h incubation with each ligand. Rosiglitazone, a PPARgamma ligand, significantly increased glucose uptake (after 24h serum pre-incubation: 24h P=0.0062, 48h P=0.0233; after 48h serum pre-incubation:24h P=0.0051,48h P=0.0154,ANOVA) and lactate accumulation (after 24h serum pre-incubation:24h P<0.0001,48h P=0.0012; after 48h serum pre-incubation:24h P=0.0003,48h P<0.0001). The same significant increase was observed using PPARgamma ligand troglitazone for both glucose uptake (after 24h serum pre-incubation:24h P=0.0108,48h P=0.0059; after 48h serum pre-incubation:24h P=0.0015,48h P=0.0168) and lactate accumulation (after 24h serum pre-incubation:24h P<0.0001,48h P<0.0001; after 48h serum pre-incubation:24h P<0.0001,48h P=0.0001). The RXR ligand, LG-retinoid increased glucose uptake (after 24h serum pre-incubation:48h P=0.0148; after 48h serum pre-incubation:24h P=0.0243) and lactate accumulation (after 24h serum pre-incubation:24h P<0.0001,48h P=0.0008; after 48h serum pre-incubation:24h P=0.0005). These results clearly demonstrate that the PPARgamma/RXR heterodimer and its ligands mediate glucose uptake metabolism in human granulosa cells. This work was supported by Wellbeing.
22 - 24 Mar 2004
British Endocrine Societies