Hum. Reprod. Advance Access originally published online on November 11, 2004
Human Reproduction 2005 20(2):373-381; doi:10.1093/humrep/deh609
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries
1 Institute of Reproductive and Developmental Biology, 2 Department of Obstetrics and Gynaecology, Imperial College London, London and 3 Clinical Chemistry Laboratory, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
5 To whom correspondence should be addressed. Email: s.franks{at}imperial.ac.uk
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<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS.
Key words: granulosa cells/insulin resistance/LH/polycystic ovaries/progesterone
4 Present address: Department of Basic Medical Sciences, St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, UK
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Palomba, A. Falbo, F. Zullo, and F. Orio Jr. Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review Endocr. Rev., February 1, 2009; 30(1): 1 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Richardson, S. Ingamells, C. D. Simonis, I. T. Cameron, R. Sreekumar, A. Vijendren, L. Sellahewa, S. Coakley, and C. D. Byrne Stimulation of Lactate Production in Human Granulosa Cells by Metformin and Potential Involvement of Adenosine 5' Monophosphate-Activated Protein Kinase J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 670 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kenigsberg, Y. Bentov, V. Chalifa-Caspi, G. Potashnik, R. Ofir, and O. S. Birk Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients Mol. Hum. Reprod., February 1, 2009; 15(2): 89 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dorfman, V. D. Ramirez, E. Stener-Victorin, and H. E. Lara Chronic-Intermittent Cold Stress in Rats Induces Selective Ovarian Insulin Resistance Biol Reprod, February 1, 2009; 80(2): 264 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Franks, J. Stark, and K. Hardy Follicle dynamics and anovulation in polycystic ovary syndrome Hum. Reprod. Update, May 22, 2008; (2008) dmn015v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A Forsdike, K. Hardy, L. Bull, J. Stark, L. J Webber, S. Stubbs, J. E Robinson, and S. Franks Disordered follicle development in ovaries of prenatally androgenized ewes J. Endocrinol., February 1, 2007; 192(2): 421 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Poretsky Polycystic Ovary Syndrome--Increased or Preserved Ovarian Sensitivity to Insulin? J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2859 - 2860. [Full Text] [PDF]
|
|
|
|
|
|
S. C. Foong, D. H. Abbott, M. A. Zschunke, T. G. Lesnick, J. L. Phy, and D. A. Dumesic Follicle Luteinization in Hyperandrogenic Follicles of Polycystic Ovary Syndrome Patients Undergoing Gonadotropin Therapy for in Vitro Fertilization J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2327 - 2333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Palomba, A. Falbo, F. Orio Jr, F. Manguso, T. Russo, A. Tolino, C. Annamaria, B. Dale, and F. Zullo A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination Hum. Reprod., October 1, 2005; 20(10): 2879 - 2886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.H. Abbott, D.K. Barnett, C.M. Bruns, and D.A. Dumesic Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum. Reprod. Update, July 1, 2005; 11(4): 357 - 374. [Abstract] [Full Text] [PDF]
|
|