Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 6 OC13

SFE2003 Oral Communications Reproduction (8 abstracts)

Resistance to insulin-dependent glucose metabolism in human granulosa-luteal cells from anovulatory women with polycystic ovaries

S Rice , N Christoforides , C Gadd , D Nickolaou , L Seyani , M Donaldson , R Margara , K Hardy & S Franks

Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

Insulin resistance and hyperinsulinaemia are well-recognised characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study was that insulin resistance in the ovary is pathway-specific i.e. is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism) whereas its steroidogenic action remains intact. Granulosa-luteal (GL) cells were obtained (with local Ethical Committee approval) during IVF cycles from women with normal ovaries, ovulatory (ov) and anovulatory (anov) PCO (n=7 per group). GL cells were cultured with insulin (1,10,100 & 1000ng/ml) and luteinizing hormone (LH) (1,2.5 & 5ng/ml). Media was sampled at 24 and 48 hours and analysed for glucose uptake and lactate production (the end point of anaerobic glycolysis). Progesterone production from the cells was measured at the end of the culture period. Insulin stimulated lactate production, in a dose-dependent manner, by GL cells from normal and ovPCO but not anovPCO (normal vs. anovPCO: p=0.002, ANOVA). There were no differences between the groups in insulin-stimulated glucose uptake. Nor was there a difference in insulin-stimulated progesterone production between GL cells of the 3 ovarian types. By contrast LH-stimulated progesterone production was significantly greater in GL cells from anovPCO than in normal (p=0.046) and ovPCO (p=0.019, ANOVA). In summary, GL cells from women with anovPCOS are relatively resistant to the effects of insulin stimulated glucose utilisation compared to those from normal and ovPCO whilst maintaining normal steroidogenic output in response to physiological doses of insulin, and increased P production in response to LH. This attenuation in the glucose response to insulin could lead to a reduction in the energy supply to the growing follicle; which, together with increased responsiveness to LH and androgen levels, may contribute to prematurely advanced granulosa cell differentiation and arrest of follicle growth in insulin-resistant PCOS. Supported by MRC and Wellbeing

Volume 6

194th Meeting of the Society for Endocrinology and Society for Endocrinology joint with Diabetes UK Endocrinology and Diabetes Day

Society for Endocrinology 

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