Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries

BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized 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 is that insulin res...

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Bibliographic Details
Published in:Human reproduction (Oxford) 2005-02, Vol.20 (2), p.373-381
Main Authors: Rice, S., Christoforidis, N., Gadd, C., Nikolaou, D., Seyani, L., Donaldson, A., Margara, R., Hardy, K., Franks, S.
Format: Article
Language:English
Subjects:
Adult
Anovulation - drug therapy
Anovulation - metabolism
Biological and medical sciences
Female
Female genital diseases
Follicle Stimulating Hormone - administration & dosage
Glucose - pharmacokinetics
granulosa cells
Gynecology. Andrology. Obstetrics
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - metabolism
Insulin - administration & dosage
Insulin - metabolism
Insulin Resistance
Lactic Acid - metabolism
Luteal Cells - metabolism
Luteinizing Hormone - administration & dosage
Luteinizing Hormone - metabolism
Medical sciences
Non tumoral diseases
Ovulation Induction - methods
polycystic ovaries
Polycystic Ovary Syndrome - metabolism
progesterone
Progesterone - metabolism
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Summary:BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized 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 is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/deh609