Effect of Testosterone Enanthate Modeling of Polycystic Ovary on Liver Irs-2 mRNA Expression in Rats: A Brief Report

Main Article Content

Seyyed Amir Yasin Ahmadi
Mandana Beigi Boroujeni
Naser Pajouhi
Amin Hasanvand
Afshin Hasanvand
Seyed Behnamedin Jamei
Asghar Aaliehpour
Reza Nekouian


There are many animal models for polycystic ovary (PCO); using exogenous testosterone enanthate is one of the methods of induction of these models. However, induction of insulin resistance should also be studied in the modeling technics. Therefore, the present study aims to investigate the expression of insulin receptor substrate (Irs)-2 mRNA in the liver tissue of rat PCO model. Nineteen Wistar rats were divided into three groups; (1) PCO modeling group (N =7) received daily 1.0 mg/100g testosterone enanthate solved in olive oil along with free access dextrose water 5%, (2) vehicle group (N =6), which handled like the PCO group, but did not receive testosterone enanthate, (3) control group (N =6) with standard care. All the animals were administered via intra-peritoneal injection for 14 days. Expression of Irs-2 mRNA was studied with real-time PCR and fold changes (FC) were reported. The average of expression in the control group was considered as the calibrator. About 13.4% expression reduction was found in the PCO group (FC =0.874, P-value =0.043). No significant reduction was found in the vehicle group (FC =0.951, P-value =0.076). However, analysis of variance did not show a significant difference between all the groups of study (P-value =0.085). The present model of PCO might induce insulin resistance at liver level with a low effect size via reduction in the mRNA expression of Irs-2. Study of the involved genes and molecules in other tissues of PCO animal models is suggested.


Download data is not yet available.

Article Details

How to Cite
Ahmadi SAY, Beigi Boroujeni M, Pajouhi N, Hasanvand A, Hasanvand A, Jamei SB, Aaliehpour A, Nekouian R. Effect of Testosterone Enanthate Modeling of Polycystic Ovary on Liver Irs-2 mRNA Expression in Rats: A Brief Report. Baghdad Sci.J [Internet]. 2021 Sep. 1 [cited 2022 Dec. 4];18(3):0480. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/5343


Xing L-J, Zhang L, Liu T, Hua Y-Q, Zheng P-Y, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol. 2011;668(3):467-71.

Previs SF, Withers DJ, Ren J-M, White MF, Shulman GI. Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. Journal of Biological Chemistry. 2000;275(50):38990-4.

Kiani F, Sayehmiri F, Hasanpour Dehkordi A, Motedayen M. Surveying the relationship between Gly1057Asp polymorphism of IRS-2 gene and susceptibility to type 2 diabetes; a systematic review and meta-analysis study. J Renal Inj Prev. 2019;8(4):263-70.

Keshavarz M, Moradi S, Emami Z, Rohani F. Association between serum 25 (OH) vitamin D and metabolic disturbances in polycystic ovary syndrome. Neth J Med. 2017;5:191-6.

Delitala AP, Capobianco G, Delitala G, Cherchi PL, Dessole S. Polycystic ovary syndrome, adipose tissue and metabolic syndrome. Arch. Gynecol. Obstet. 2017;296(3):405-19.

Glintborg D, Andersen M. MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome. Eur J Endocrinol. 2017;176(2):R53-R65.

Pasquali R. Metabolic syndrome in polycystic ovary syndrome. Metabolic Syndrome Consequent to Endocrine Disorders. 49: Karger Publishers; 2018. p. 114-30.

Darabi S, Hasanvand A. Protective effect of metformin on diabetes mellitus, diabetic kidney disease and hepatocytes. Annals of Research in Antioxidants. 2018;3(1):e03.

Sadeghi H, Jahanbazi F, Sadeghi H, Omidifar N, Alipoor B, Kokhdan EP, et al. Metformin attenuates oxidative stress and liver damage after bile duct ligation in rats. Res Pharm Sci. 2019;14(2):122.

Ainehchi N, Farshbaf-Khalili A, Ghasemzadeh A, Hamdi K, Khaki A, Ouladsahebmadarek E, et al. The Effect of Herbal Medicine Supplementation on Clinical and Para-clinical Outcomes in Women With PCOS: A Systematic Review and Meta-analysis. Int J Wom Health Reprod Sci. 2017;7(4):423-33.

Khan AA, Begum W. Efficacy of Darchini in the management of polycystic ovarian syndrome: A randomized clinical study. Journal of Herbal Medicine. 2019;15:100249.

Arentz S, Smith CA, Abbott J, Fahey P, Cheema BS, Bensoussan A. Combined lifestyle and herbal medicine in overweight women with polycystic ovary syndrome (PCOS): A randomized controlled trial. Phytother Res. 2017;31(9):1330-40.

Wiweko B, Susanto CA. The effect of metformin and cinnamon on serum anti-mullerian hormone in women having PCOS: A Double-blind, randomized, controlled trial. JHRS. 2017;10(1):31.

Corbett S, Morin-Papunen L. The polycystic ovary syndrome and recent human evolution. Mol Cell Endocrinol. 2013;373(1-2):39-50.

Speca S, Napolitano C, Tagliaferri G. The pathogenetic enigma of polycystic ovary syndrome. J Ultrasound. 2007;10(4):153-60.

Lujan ME, Chizen DR, Pierson RA. Diagnostic criteria for polycystic ovary syndrome: pitfalls and controversies. J Obstet Gynaecol Can. 2008;30(8):671-9.

Osuka S, Nakanishi N, Murase T, Nakamura T, Goto M, Iwase A, et al. Animal models of polycystic ovary syndrome: A review of hormone‐induced rodent models focused on hypothalamus‐pituitary‐ovary axis and neuropeptides. Mol Cell Endocrinol. 2019;18(2):151-60.

Noroozzadeh M, Behboudi-Gandevani S, Zadeh-Vakili A, Tehrani FR. Hormone-induced rat model of polycystic ovary syndrome: A systematic review. Life sciences. 2017;191:259-72.

Oakley O, Lin P-C, Bridges P, Ko C. Animal models for the study of polycystic ovarian syndrome. Endocrinology and Metabolism. 2011;26(3):193-202.

Ahmadi M, Rostamzadeh A, Fathi F, Mohammadi M, Rezaie MJ. The effect of Melatonin on histological changes of ovary in induced polycystic ovary syndrome model in mice. Middle East Fertil Soc J . 2017 Dec 1;22(4):255-9..

Kalhori Z, Azadbakht M, Bazdar A, Zeinali H. Polycystic ovary induction in Mouse by testosterone enanthate. Journal of Fasa University of Medical Sciences. 2014;3(4):387-91.

Noori F, Azadbakht M, Parto P, Bazaz Z. The Effect of Repaglinide on Polycystic Ovary Induced by Testosterone Enanthate in NMRI Mice. Journal of Fasa University of Medical Sciences. 2017;6(4):446-73.

Ghowsi M, Yousofvand N, Moradi S. Effects of Salvia officinalis L.(common sage) leaves tea on insulin resistance, lipid profile, and oxidative stress in rats with polycystic ovary: An experimental study. Avicenna J Phytomed. 2020;10(3):263-72.

Jeckel KM, Bouma GJ, Hess AM, Petrilli EB, Frye MA. Dietary fatty acids alter left ventricular myocardial gene expression in Wistar rats. Nutrition research. 2014;34(8):694-706.

Gyte A, Pritchard L, Jones H, Brennand J, White A. Reduced Expression of the KATP Channel Subunit, Kir6. 2, is Associated with Decreased Expression of Neuropeptide Y and Agouti‐Related Protein in the Hypothalami of Zucker Diabetic Fatty Rats. Journal of neuroendocrinology. 2007;19(12):941-51.

Demissie M, Lazic M, Foecking EM, Aird F, Dunaif A, Levine JE. Transient prenatal androgen exposure produces metabolic syndrome in adult female rats. Am J Physiol Endocrinol Metab. 2008;295(2):E262-E8.

Zhang J, Ou J, Bashmakov Y, Horton JD, Brown MS, Goldstein JL. Insulin inhibits transcription of IRS-2 gene in rat liver through an insulin response element (IRE) that resembles IREs of other insulin-repressed genes. Proceedings of the National Academy of Sciences. 2001;98(7):3756-61.

Dominici F, Hauck S, Argentino D, Bartke A, Turyn D. Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice. Journal of Endocrinology. 2002;173(1):81-94.

Yen H, Jakimiuk A, Munir I, Magoffin D. Selective alterations in insulin receptor substrates-1,-2 and-4 in theca but not granulosa cells from polycystic ovaries. MHR: Basic science of reproductive medicine. 2004;10(7):473-9.

Baranova A, Tran T, Birerdinc A, Younossi Z. Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non‐alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011;33(7):801-14.

Burks DJ, de Mora JF, Schubert M, Withers DJ, Myers MG, Towery HH, et al. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature. 2000;407(6802):377.