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Glutathione S-transferase (GST) polymorphism could be an early marker in the development of polycystic ovary syndrome (PCOS) — an insight from non-obese and non-insulin resistant adolescents
Affiliations- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia, Serbia and Montenegro
open access
Abstract
Introduction: It has been supposed that endocrine disturbances might be responsible for polycystic ovary syndrome (PCOS)-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinemic adolescent girls newly diagnosed with PCOS.
Materials and methods: Nitrotyrosine, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR.
Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosine concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype.
Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS.
Abstract
Introduction: It has been supposed that endocrine disturbances might be responsible for polycystic ovary syndrome (PCOS)-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinemic adolescent girls newly diagnosed with PCOS.
Materials and methods: Nitrotyrosine, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR.
Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosine concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype.
Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS.
Keywords
oxidative stress, nitrotyrosine, testosterone, hyperandrogenism, polycystic ovary syndrome
About this articleTitle
Glutathione S-transferase (GST) polymorphism could be an early marker in the development of polycystic ovary syndrome (PCOS) — an insight from non-obese and non-insulin resistant adolescents
Journal
Issue
Article type
Original paper
Pages
366-374
Published online
2018-06-01
Page views
1957
Article views/downloads
1359
DOI
10.5603/EP.a2018.0034
Pubmed
Bibliographic record
Endokrynol Pol 2018;69(4):366-374.
Keywords
oxidative stress
nitrotyrosine
testosterone
hyperandrogenism
polycystic ovary syndrome
Authors
Ana Savić-Radojević
Ilijana Mažibrada
Tatjana Djukić
Zoran B. Stanković
Marija Plješa-Ercegovac
Katarina Sedlecky
Jelica Bjekić-Macut
Tatjana Simić
George Mastorakos
Djuro Macut
References (32)- Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1): 19–25.
- Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010; 203(3): 201.e1–201.e5.
- Conway G, Dewailly D, Diamanti-Kandarakis E, et al. ESE PCOS Special Interest Group. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol. 2014; 171(4): P1–29.
- Catteau-Jonard S, Dewailly D. Pathophysiology of polycystic ovary syndrome: the role of hyperandrogenism. Front Horm Res. 2013; 40: 22–27.
- Dewailly D, Lujan ME, Carmina E, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2014; 20(3): 334–352.
- Barber TM, Franks S. Genetics of polycystic ovary syndrome. Front Horm Res. 2013; 40: 28–39.
- Macut D, Bjekić-Macut J, Savić-Radojević A. Dyslipidemia and oxidative stress in PCOS. Front Horm Res. 2013; 40: 51–63.
- Agarwal A, Aponte-Mellado A, Premkumar BJ, et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012; 10: 49.
- González F, Rote NS, Minium J, et al. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006; 91(1): 336–340.
- Azziz R, Adashi EY. Stein and Leventhal: 80 years on. Am J Obstet Gynecol. 2016; 214(2): 247.e1–247.e11.
- Savic-Radojevic A, Bozic Antic I, Coric V, et al. Effect of hyperglycemia and hyperinsulinemia on glutathione peroxidase activity in non-obese women with polycystic ovary syndrome. Hormones (Athens). 2015; 14(1): 101–108.
- Laven JSE, Imani B, Eijkemans MJC, et al. New approach to polycystic ovary syndrome and other forms of anovulatory infertility. Obstet Gynecol Surv. 2002; 57(11): 755–767.
- Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961; 21: 1440–1447.
- Balen AH, Laven JSE, Tan SL, et al. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update. 2003; 9(6): 505–514.
- Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7): 412–419.
- Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22(9): 1462–1470.
- Günzler WA, Kremers H, Flohé L. An improved coupled test procedure for glutathione peroxidase (EC 1-11-1-9-) in blood. Z Klin Chem Klin Biochem. 1974; 12(10): 444–448.
- Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972; 247(10): 3170–3175.
- Abdel-Rahman SZ, el-Zein RA, Anwar WA, et al. A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies. Cancer Lett. 1996; 107(2): 229–233.
- Ping J, Wang H, Huang M, et al. Genetic analysis of glutathione S-transferase A1 polymorphism in the Chinese population and the influence of genotype on enzymatic properties. Toxicol Sci. 2006; 89(2): 438–443.
- González F, González F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012; 77(4): 300–305.
- Macut D, Simic T, Lissounov A, et al. Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress. Exp Clin Endocrinol Diabetes. 2011; 119(7): 451–455.
- Victor VM, Rocha M, Bañuls C, et al. Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab. 2009; 94(9): 3505–3512.
- Jiang F, Zhang Y, Dusting GJ. NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev. 2011; 63(1): 218–242.
- Chignalia AZ, Oliveira MA, Debbas V, et al. Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms. Clin Sci (Lond). 2015; 129(1): 39–48.
- Tosi F, Bonora E, Moghetti P. Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes. Hum Reprod. 2017; 32(12): 2515–2521.
- Parker L, Shaw CS, Stepto NK, et al. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling. Front Endocrinol (Lausanne). 2017; 8: 87.
- Pessin JE, Saltiel AR. Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest. 2000; 106(2): 165–169.
- Sies H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol. 2017; 11: 613–619.
- Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 2000; 61(3): 154–166.
- Wu B, Dong D. Human cytosolic glutathione transferases: structure, function, and drug discovery. Trends Pharmacol Sci. 2012; 33(12): 656–668.
- Pittaluga M, Sgadari A, Dimauro I, et al. Physical exercise and redox balance in type 2 diabetics: effects of moderate training on biomarkers of oxidative stress and DNA damage evaluated through comet assay. Oxid Med Cell Longev. 2015; 2015: 981242.
