Methyltrienolone influences on the androgen receptors and DNA&RNA synthesis in the liver cells of male rats with alloxan-induced diabetes

Sopiko Kandelaki, Neli Didebulidze, Manana Kakabadze, Salome Kordzaia, Jordi Muntané Relat, Javier Padillo

Abstract


Introduction: It has been revealed previously, that metabolic imbalances during the diabetes, occurring with multi-organ participation, are accompanied by the decrease of corticosterone concentration in blood and with the depression of DNA & RNA synthesis, and as well as expression of androgen receptors in liver cells.

Aim: The purpose of our study was to examine how exogenous testosterone can correct mentioned liver cell disturbances under the conditions of experimental diabetes.

Methods: The concentrations of glucose, immune-reactive insulin and testosterone were examined in blood in parallel with studying of histology of pancreatic islets - on the 15th, 30th and 45th days from intraperitoneal injection of Alloxan -  to confirm the development of adequate model of experimental (alloxan-induced)  Diabetes in Wistar Rats aged 2 months and weighting 180-200 g. DNA and RNA synthesis, proliferative activity and androgen receptor expression in the hepatic cells were studied on the same terms of the experiment – to confirm the involvement of liver in diabetes-caused metabolic disturbances. All above-mentioned  investigations were repeated in animals undergone to exposure of exogenous synthetic androgen – methyltrienolone during 15 days – beginning from 31st day of Alloxan-induced diabetes.      

Results: Methyltrienolone supplementation reduces the alterations of blood concentration of immune-reactive insulin, glucose and testosterone and supports the regeneration of androgen receptors’ expression and DNA/RNA synthesis in hepatocytes. However, the increase of nuclear acids synthesis is accompanied by increase of hepatocytes ploidy but not their proliferation.

Conclusion: The administration of methyltrienolone reduces the effect of “diabetic stress”. Its influence on DNA/RNA synthesis in hepatocytes might be realized through the regeneration of active androgen receptors of liver cells.  


Keywords


Alloxan-induced diabetes, testosterone, liver androgen receptors, DNA, RNA, Pancreatic β-cells disturbance

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References


Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, MacIsaac RJ, Clarke S, Zajac JD, Jerums G. Low testosterone levels are common and associated with insulin resistance in men with diabetes. The journal of clinical endocrinology & metabolism. 2008 May;93(5):1834-40.

Holt SK, Lopushnyan N, Hotaling J, Sarma AV, Dunn RL, Cleary PA, Braffett BH, Gatcomb P, Martin C, Herman WH, Wessells H. Prevalence of low testosterone and predisposing risk factors in men with type 1 diabetes mellitus: findings from the DCCT/EDIC. The Journal of Clinical Endocrinology & Metabolism. 2014 Jul 11;99(9):E1655-60.

Didebulidze NA, Kakabadze MS, Gordadze NG, Latsabidze IN, Kordzaya ME, Sikharulidze IT. Correction of Hormonal and Metabolic Disorders in Male Rats with Developing Experimental Diabetes. Bulletin of experimental biology and medicine. 2015 May 1;159(1):20.

Zhang Y, Klein K, Sugathan A, Nassery N, Dombkowski A, Zanger UM, Waxman DJ. Transcriptional profiling of human liver identifies sex-biased genes associated with polygenic dyslipidemia and coronary artery disease. PLoS One. 2011 Aug 12;6(8):e23506.

Dulbecco R, Hartwell LH, Vogt M. Induction of cellular DNA synthesis by polyoma virus. Proceedings of the National Academy of Sciences. 1965 Feb 1;53(2):403-10.

Kandeel FR, Swerdloff RS, Pryor JL, editors. Male Reproductive Dysfunction: Pathophysiology and Treatment. CRC Press; 2007 May 22.

Francés DE, Ronco MT, Monti JA, Ingaramo PI, Pisani GB, Parody JP, Pellegrino JM, Sanz PM, Carrillo MC, Carnovale CE. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect. Journal of Endocrinology. 2010 May 1;205(2):187-200.

Moudgil VK. Phosphorylation of steroid hormone receptors. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1990 Dec 10;1055(3):243-58.


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