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Objective: To investigate the role of serum total testsoterone levels and androgen receptors in diabetic rats with erectile dysfunction and to contribute to the development of the new treatment strategies for these diseases based on common pathogenesis.
Material and Methods: In the study, we used 8 rats in the control group, 8 rats in diabetes mellitus (DM) group and 8 rats in castration group. In the control group (Group 1) rats were formed entirely healthy male rats. In the DM group (Group 2), DM was induced by streptozotocin injection. In castration group (Group 3), rats underwent bilateral orchiectomy. In all groups, weight, serum total testosterone level and intracavernosal pressure, mean arterial pressure ratios (ICP / MAP) was measured. Rats were sacrificed at the 3rd week of the study in Group 1, at the 3rd week of castration in Group 3 and at the 6th week of the DM formation in Group 2. After that, pancreas, prostate, corpus cavernosum and testicular tissue was dissected and immunohistochemical staining for androgen receptor examination was performed.
Results: The median serum total testosterone levels for Group 1, 2 and 3 were 2.5±0.92; 0.46±0.17 and 0.1 ng/ml respectively. Groups 2 and 3, serum total testosterone levels was significantly lower compared with Group 1 (p<0.01). No statistically significant difference showed between Group 2 and 3 (p=0.41). AR expression is compared between groups 1 and 2; no changes in the corpus cavernosum and the prostate, increased expression in pancreas langerhans islets and decreased expression in the testis were found.
Conclusion: According to our results, serum total testosterone level decreased significantly in diabetic rats with ED, AR expression did not change in the prostate and corpus cavernosum, increased in the pancreatic langerhans islet cells and decreased in the testis.
2. Aytac I, McKinlay J, Krane R. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999;84:50-6.
3. Mikhail N. Does testosterone have a role in erectile function? American J Med. 2006;119:373-82.
4. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: an overview. Endocr Rev 2002;23:175-200.
5. Yong EL, Lim J, Qi W, Ong V, Mifsud A. Molecular basis of androgen receptor diseases. Ann Med. 2000;32:15-22.
6. Corona G, Mannucci E, Mansani R, Petrone L, Bartolini M, Giommi R, et al. Organic, relational and psychological factors in erectile dysfunction in men with diabetes mellitus. Eur Urol 2004;46:222-8.
7. Aslan Y, Guzel O, Balci M, Tuncel A, Yildiz M, Atan A. The impact of metabolic syndrome on serum total testosterone level in patients with erectile dysfunction. Aging Male 2014;17:76-80.
8. Yu I-C, Lin H-Y, Sparks JD, Yeh S, Chang C. Androgen receptor roles in insulin resistance and obesity in males: the linkage of androgendeprivation therapy to metabolic syndrome. Diabetes 2014;63:3180-8.
9. Stanworth R, Kapoor D, Channer K, Jones T. Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes. Eur J Endocrinol 2008;159:739-46.
10. Akbarzadeh A, Norouzian D, Mehrabi M, Jamshidi S, Farhangi A, Verdi AA, et al. Induction of diabetes by treptozotocin in rats. Indian J Clin Biochem 2007;22:60-4.
11. Arcolino FO, Ribeiro DL, Gobbo MG, Taboga SR, Goes RM. Proliferation and apoptotic rates and increased frequency of p63-positive cells in the prostate acinar epithelium of alloxan-induced diabetic rats. Int J Exp Pathol 2010;91:144-54.
12. Bivalacqua T, Usta M, Champion H, Leungwattanakij S, Dabisch P, McNamara D, ve ark. Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 2004;16:21-9.
13. Cakalağaoğlu F. Tissue processing. Aegean Pathology Journal 2005;2:29-34.
14. Matsuda Y, Fujii T, Suzuki T, Yamahatsu K, Kawahara K, Teduka K, ve ark. Comparison of fixation methods for preservation of morphology, RNAs, and proteins from paraffin-embedded human cancer cell-implanted mouse models. J
Histochem Cytochem 2011;59:68-75.
15. Brown RW, Chirala R. Utility of microwavecitrate antigen retrieval in diagnostic immunohistochemistry. Mod pathol 1995;:515-20.
16. Goldstein M, Watkins S. Immunohistochemistry.28 วารสาร ยูโร : ปีที่ 40 ฉบับที่ 2 กรกฎาคม - ธันวาคม 2562 Curr Protoc Mol Bio 2008:14-6.
17. Mori R, Wang Q, Quek ML, Tarabolous C, Cheung E, Ye W, et al. Prognostic value of the androgen receptor and its coactivators in patients with D1 prostate cancer. Anticancer Research 2008;28:425-30.
18. Edition IDAS. International Diabetes Federation 2013. Update. 2014.
19. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
20. Vernet D, Cai L, Garban H, Babbitt ML, Murray FT, Rajfer J, et al. Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and BBZ/WORdp (type II) rats with erectile dysfunction. Endocrinology 1995;136:5709-17.
21. Baba K, Yajima M, Carrier S, Akkus E, Reman J, Nunes L, et al. Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Urology 2000;56:533-8.
22. Porst H, Oelke M, Goldfischer ER, Cox D, Watts S, Dey D, et al. Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4
multinational, randomized, placebo-controlled clinical studies. Urology 2013;82:667-73.
23. Rhoden EL, Ribeiro EP, Teloken C, Souto CA. Diabetes mellitus is associated with subnormal serum levels of free testosterone in men. BJU Int 2005;96:867-70.
24. Ghazi S, Zohdy W, Elkhiat Y, Shamloul R. Serum testosterone levels in diabetic men with and without erectile dysfunction. Andrologia 2012;44:373-80.
25. Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 2004;89:5462-8.
26. Chamness S, Ricker D, Crone J, Dembeck C, Maguire M, Burnett A, et al. The effect of androgen on nitric oxide synthase in the male reproductive tract of the rat. Fertil Steril. 1995;63:1101-7.
27. Chang C, Kokontis J, Liao S. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 1988;240:324-6.
28. Beilin J, Ball E, Favaloro J, Zajac J. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol 2000;25:85-96.
29. Suzuki K, Ito K, Kurokawa K, Suzuki T, Shimizu N, Fukabori Y, et al. Expression and degradation of rat androgen receptor following castration, testosterone replacement and antiandrogens administration: analysis by Western blot and
immunohistochemistry. Tohoku J Exp Med 1997;183:159-72.
30. Yamanaka M, Shirai M, Shiina H, Tanaka Y, Tsujimura A, Matsumiya K, ve ark. Diabetes induced erectile dysfunction and apoptosis in penile crura are recovered by insulin treatment in rats. J Urol 2003;170:291-7.
31. Takane KK, George FW, Wilson JD. Androgen receptor of rat penis is down-regulated by androgen. Am J Physiol Endocrinol Metab 1990;258:46-50.
32. Li R-J, Qiu S-D, Wang H-X, Tian H, Wang L-R, Huo Y-W. Androgen receptor: a new player associated with apoptosis and proliferation of pancreatic beta-cell in type 1 diabetes mellitus. Apoptosis 2008;13:959-71.
33. Morimoto S, Mendoza-Rodriguez C, Hiriart M, Larrieta M, Vital P, Cerbon M. Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas. J Endocrinol 2005;187:217-24.