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

Rice, Suman; Christoforidis, Nikolaos; Gadd, C.; Nikolaou, Dimitrios; Seyani, L.; Donaldson, A.; Margara, R.; Hardy, Kate; Franks, Stephen

doi:10.1093/humrep/deh609

Cited by 185 publications

(122 citation statements)

References 51 publications

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“…As case 1 had a smaller r (X) chromosome compared to case 2, we analysed the additional genes deleted and found that the extra region deleted in case 1 (Xq21.33-Xq22.1) were harbouring genes involved in thyroid hormone signalling, insulin receptor signalling, meiosis regulation, cell cycle regulation and chromatin organization. Alterations in these pathways are reported to be responsible for ovarian dysfunction [1,5,9,31,36,46].…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

Chauhan

Jaiswal

Lakhotia

et al. 2016

J Assist Reprod Genet

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Purpose In the present study, we reported two cases of TS with mosaic ring X chromosome showing common clinical characteristics of TS like growth retardation and ovarian dysfunction. The purpose of the present study was to cytogenetically characterize both cases. Methods Whole blood culture and G-banding were performed for karyotyping the cases following standard protocol. Origin of the ring chromosome and degree of mosaicism were further determined by fluorescence in situ hybridization (FISH). Breakpoints and loss of genetic material in formation of different ring X chromosomes r (X) in cases were determined with the help of cytogenetic microarray. Results Cases 1 and 2 with ring chromosome were cytogenetically characterized as 45, X [114]/46Xr (X) (p22.11q21.32) [116] and 45, X [170]/46, Xr (X) (p22.2q21.33) [92], respectively. Sizes of these ring X chromosomes were found to be~7 5 and~95 Mb in cases 1 and 2, respectively, using visual estimation as part of cytogenetic observation. In both cases, we observed breakpoints on Xq chromosome were within relatively narrow region between Xq21.33 and Xq22.1 compared to regions in previously reported cases associated with ovarian dysgenesis. Conclusions Our observation agrees with the fact that despite of large heterogeneity, severity of the cases with intact Xinactive specific transcript (XIST) is dependent on degree of mosaicism and extent of Xq deletion having crucial genes involved directly or indirectly in various physiological involving ovarian cyclicity.

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Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

Chauhan

Jaiswal

Lakhotia

et al. 2016

J Assist Reprod Genet

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“…The intra-assay coefficient of variations were 6 . 4% (Rice et al 2005) and 8 . 7% for progesterone and androstenedione respectively.…”

Section: Hormone Concentrations In Culture Mediummentioning

confidence: 96%

“…Progesterone and androstenedione concentrations were measured in samples of medium collected from ovarian cortex cultures using commercially available kits (Coat-aCount; Diagnostic Products Corp., Los Angeles, CA, USA) by methods previously described (Rice et al 2005). Samples of medium were pooled from days 0-5, 6-10 and 11-15 for each animal and steroid production during each time period analysed.…”

Section: Hormone Concentrations In Culture Mediummentioning

confidence: 99%

Disordered follicle development in ovaries of prenatally androgenized ewes

Forsdike¹,

Hardy²,

Bull³

et al. 2007

Journal of Endocrinology

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Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm 3

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“…31 It may seem paradoxical that insulin appears to contribute to abnormal ovarian follicular function in PCOSFa state of peripheral insulin resistanceFbut recent data suggest that insulin resistance in the ovary is signalling pathway specific. Glucose uptake and metabolism by granulosa-lutein cells have been shown to be impaired [32][33][34] but the steroidogenic response is maintained. 34 Interaction of genes and environment in aetiology of PCOS Genetic factors.…”

Section: Introductionmentioning

confidence: 99%

“…Glucose uptake and metabolism by granulosa-lutein cells have been shown to be impaired [32][33][34] but the steroidogenic response is maintained. 34 Interaction of genes and environment in aetiology of PCOS Genetic factors. There is now compelling evidence that genetic factors are important in the aetiology of PCOS.…”

Section: Introductionmentioning

confidence: 99%

Polycystic ovary syndrome in adolescents

2008

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Background: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women and typically presents during adolescence. The clinical and biochemical presentation is heterogeneous, but elevated serum concentrations of androgens are the most consistent biochemical abnormality and may be considered to be the hallmark of the syndrome. Many women with PCOS also have insulin resistance and hyperinsulinaemia, which may contribute to the clinical and endocrine abnormalities. The aetiology of PCOS is not clear but studies in the Rhesus monkey suggest that exposure to excess androgen during intrauterine life results in many of the features of human PCOS, including ovarian dysfunction, abnormal LH secretion and insulin resistance. Objective: To review the studies from the literature, including those of the author, regarding aetiology, presentation and management of PCOS in adolescents. Results and conclusions: We have proposed that PCOS in adolescents arises as a result of a genetically determined disorder of ovarian function that results in hyper-secretion of androgens, possibly during fetal life and also during physiological activation of the hypothalamic-pituitary-ovarian in infancy and at the onset of puberty. There is plentiful evidence for a genetic basis for PCOS (it appears to be a complex endocrine disorder resulting from the effects of a several genes), but environmental factors, notably nutrition, influence the clinical and biochemical phenotype. Obesity unmasks or amplifies symptoms, endocrine and metabolic abnormalities. The increasing incidence of childhood obesity has resulted in an alarming Increase not only in distressing symptoms but also impaired glucose tolerance and even diabetes among adolescent girls with PCOS. The search for PCOS genes in this condition, that is not only heterogeneous but also presents only in women of reproductive age, is not straightforward and has produced few convincing candidates so far. In due course, however, identification of the major susceptibility loci is likely to provide key insight into the aetiology of the syndrome and improve diagnosis and management.

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

Cited by 185 publications

References 51 publications

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

Disordered follicle development in ovaries of prenatally androgenized ewes

Polycystic ovary syndrome in adolescents

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