medigraphic.com
ISSN 2395-8723 (Electronic)
ISSN 1405-888X (Print)
TIP Revista Especializada en Ciencias Químico-Biológicas

2023, Number 1

<< Back Next >>

TIP Rev Esp Cienc Quim Biol 2023; 26 (1)

Testosterone treatment positively regulates protein and mRNA levels of Mn-dependent superoxide dismutase enzyme in pancreatic islets of male rats (Rattus norvegicus)

Sosa-Larios TC, Morales-Miranda A, Palomar-Morales M, Rojas-Ochoa A, Rodríguez-Peña N, Morimoto S

Language: Spanish
References: 45
Page: 1-11
PDF size: 470.60 Kb.


ABSTRACT

The androgenic hormone testosterone protects against pharmacological-induced damage to pancreatic islets in rodent models of diabetes. The increased production of reactive oxygen species damage the pancreatic islets through oxidative stress and apoptosis. The precise protective mechanism of testosterone has yet to be determined. The aim of this study was to evaluate the effect of post-gonadectomy testosterone substitution on the expression of two key antioxidant enzymes, Mn-dependent superoxide dismutase and catalase. The protein expression of the enzymes was examined by immunohistochemistry in male rats: intact, gonadectomized, and gonadectomized followed by testosterone substitution. mRNA expression was analyzed by reverse transcription-quantitative polymerase chain reaction on pancreatic islets cultured with testosterone, dihydrotestosterone (DHT) or the vehicle. Testosterone increased the protein level of MnSOD in pancreatic tissue and its mRNA expression in cultured pancreatic islets. DHT (a non-aromatizing androgen) had similar effects. For catalase, only the mRNA expression increased by testosterone treatment. Testosterone induced overexpression of MnSOD protein and mRNA in pancreatic islets through a mechanism unrelated to androgen aromatization, most likely involving androgen receptors, demonstrating the implications of testosterone in preventing damage to insulin-producing cells by oxidative stress.


REFERENCES

  1. Ahlbom, E., Prins, G. S. & Ceccatelli, S. (2001). Testosteroneprotects cerebellar granule cells from oxidative stressinducedcell death through a receptor mediated mechanism.Brain Research, 892(2), 255–262. https://doi.org/10.1016/s0006-8993(00)03155-3

  2. Alonso-Alvarez, C., Bertrand, S., Faivre, B., Chastel, O. &Sorci, G. (2007). Testosterone and oxidative stress: theoxidation handicap hypothesis. Proceedings. BiologicalSciences, 274(1611), 819–825. https://doi.org/10.1098/rspb.2006.3764

  3. Alonso-Magdalena, P., Morimoto, S., Ripoll, C., Fuentes, E.& Nadal, A. (2006). The estrogenic effect of bisphenol Adisrupts pancreatic beta-cell function in vivo and inducesinsulin resistance. Environmental Health Perspectives,114(1), 106–112. https://doi.org/10.1289/ehp.8451

  4. Beato, M. & Klug, J. (2000). Steroid hormone receptors: anupdate. Human Reproduction Update, 6(3), 225–236.https://doi.org/10.1093/humupd/6.3.225

  5. Díaz-Sánchez, V., Morimoto, S., Morales, A., Robles-Díaz, G. &Cerbón, M. (1995). Androgen receptor in the rat pancreas:genetic expression and steroid regulation. Pancreas, 11(3),241–245. https://doi.org/10.1097/00006676-199510000-00005

  6. Domingueti, C. P., Dusse, L. M., Carvalho, M.d, de Sousa, L. P.,Gomes, K. B. & Fernandes, A. P. (2016). Diabetes mellitus:The linkage between oxidative stress, inflammation,hypercoagulability and vascular complications. Journal ofDiabetes and its Complications, 30(4), 738–745. https://doi.org/10.1016/j.jdiacomp.2015.12.018

  7. Drews, G. & Düfer, M. (2012). Role of K(ATP) channels inβ-cell resistance to oxidative stress. Diabetes, Obesity &Metabolism, 14 Suppl 3, 120–128. https://doi.org/10.1111/j.1463-1326.2012.01644.x

  8. Eguchi, N., Vaziri, N. D., Dafoe, D. C. & Ichii, H. (2021). TheRole of Oxidative Stress in Pancreatic β Cell Dysfunctionin Diabetes. International Journal of Molecular Sciences,22(4), 1509. https://doi.org/10.3390/ijms22041509

  9. Guzmán, D. C., Mejía, G. B., Vázquez, I. E., García, E.H., del Angel, D. S. & Olguín, H. J. (2005). Effect oftestosterone and steroids homologues on indolaminesand lipid peroxidation in rat brain. The Journal of SteroidBiochemistry and Molecular Biology, 94(4), 369–373.https://doi.org/10.1016/j.jsbmb.2004.11.006

  10. Hammond, J., Le, Q., Goodyer, C., Gelfand, M., Trifiro, M. &LeBlanc, A. (2001). Testosterone-mediated neuroprotectionthrough the androgen receptor in human primary neurons.Journal of Neurochemistry, 77(5), 1319–1326. https://doi.org/10.1046/j.1471-4159.2001.00345.x

  11. Hanchang, W., Semprasert, N., Limjindaporn, T., Yenchitsomanus,P. T. & Kooptiwut, S. (2013). Testosterone protects againstglucotoxicity-induced apoptosis of pancreatic β-cells(INS-1) and male mouse pancreatic islets. Endocrinology,154(11), 4058–4067. https://doi.org/10.1210/en.2013-1351

  12. Harada, N., Katsuki, T., Takahashi, Y., Masuda, T., Yoshinaga,M., Adachi, T., Izawa, T., Kuwamura, M., Nakano, Y.,Yamaji, R. & Inui, H. (2015). Androgen receptor silencesthioredoxin-interacting protein and competitively inhibitsglucocorticoid receptor-mediated apoptosis in pancreaticβ-Cells. Journal of Cellular Biochemistry, 116(6), 998–1006. https://doi.org/10.1002/jcb.25054

  13. Harada, N., Yoda, Y., Yotsumoto, Y., Masuda, T., Takahashi,Y., Katsuki, T., Kai, K., Shiraki, N., Inui, H. & Yamaji,R. (2018). Androgen signaling expands β-cell mass inmale rats and β-cell androgen receptor is degraded underhigh-glucose conditions. American journal of physiology.Endocrinology and Metabolism, 314(3), E274–E286.https://doi.org/10.1152/ajpendo.00211.2017

  14. Kapoor, D., Goodwin, E., Channer, K. S. & Jones, T. H.(2006). Testosterone replacement therapy improvesinsulin resistance, glycaemic control, visceral adiposityand hypercholesterolaemia in hypogonadal men with type2 diabetes. European Journal of Endocrinology, 154(6),899–906. https://doi-org.pbidi.unam.mx:2443/10.1530/eje.1.02166

  15. King A. J. (2012). The use of animal models in diabetes research.British Journal ofPharmacology, 166(3), 877–894. https://doi.org/10.1111/j.1476-5381.2012.01911.x

  16. Kłapcińska, B., Jagsz, S., Sadowska-Krepa, E., Górski, J.,Kempa, K. & Langfort, J. (2008). Effects of castrationand testosterone replacement on the antioxidant defensesystem in rat left ventricle. The Journal of PhysiologicalSciences: JPS, 58(3), 173–177. https://doi.org/10.2170/physiolsci.RP002208

  17. Koukoulis, G. N., Filiponi, M., Gougoura, S., Befani, C.,Liakos, P. & Bargiota, Α. (2022). Testosterone anddihydrotestosterone modulate the redox homeostasis ofendothelium. Cell Biology International, 46(4), 660–670.https://doi.org/10.1002/cbin.11768

  18. Lee, Y. E., Kim, J. W., Lee, E. M., Ahn, Y. B., Song, K. H.,Yoon, K. H., Kim, H. W., Park, C. W., Li, G., Liu, Z. &Ko, S. H. (2012). Chronic resveratrol treatment protectspancreatic islets against oxidative stress in db/db mice.PLOS ONE, 7(11), e50412. https://doi.org/10.1371/journal.pone.0050412

  19. Lenzen S. (2017). Chemistry and biology of reactive specieswith special reference to the antioxidative defence status inpancreatic β-cells. Biochimica et Biophysica Acta. GeneralSubjects, 1861(8), 1929–1942. https://doi.org/10.1016/j.bbagen.2017.05.013

  20. Le May, C., Chu, K., Hu, M., Ortega, C. S., Simpson, E. R.,Korach, K. S., Tsai, M. J. & Mauvais-Jarvis, F. (2006).Estrogens protect pancreatic beta-cells from apoptosisand prevent insulin-deficient diabetes mellitus in mice.Proceedings of the National Academy of Sciences of theUnited States of America, 103(24), 9232–9237. https://doi.org/10.1073/pnas.0602956103

  21. Li, R. J., Qiu, S. D., Wang, H. X., Tian, H., Wang, L. R. & Huo,Y. W. (2008). Androgen receptor: a new player associatedwith apoptosis and proliferation of pancreatic beta-cell intype 1 diabetes mellitus. Apoptosis: an International Journalon Programmed Cell Death, 13(8), 959–971. https://doi.org/10.1007/s10495-008-0230-9

  22. Lin, B., Wang, J., Hong, X., Yan, X., Hwang, D., Cho, J. H.,Yi, D., Utleg, A. G., Fang, X., Schones, D. E., Zhao, K.,Omenn, G. S. & Hood, L. (2009). Integrated expressionprofiling and ChIP-seq analyses of the growth inhibitionresponse program of the androgen receptor. PLOS ONE,4(8), e6589. https://doi.org/10.1371/journal.pone.0006589

  23. Meydan, S., Kus, I., Tas, U., Ogeturk, M., Sancakdar, E.,Dabak, D. O., Zararsız, I. & Sarsılmaz, M. (2010).Effects of testosterone on orchiectomy-induced oxidativedamage in the rat hippocampus. Journal of ChemicalNeuroanatomy, 40(4), 281–285. https://doi.org/10.1016/j.jchemneu.2010.07.006

  24. Mizukami, H., Takahashi, K., Inaba, W., Tsuboi, K., Osonoi,S., Yoshida, T. & Yagihashi, S. (2014). Involvement ofoxidative stress-induced DNA damage, endoplasmicreticulum stress, and autophagy deficits in the decline ofβ-cell mass in Japanese type 2 diabetic patients. DiabetesCare, 37(7), 1966–1974. https://doi.org/10.2337/dc13-2018

  25. Morimoto, S., Fernandez-Mejia, C., Romero-Navarro,G., Morales-Peza, N. & Díaz-Sánchez, V. (2001).Testosterone effect on insulin content, messengerribonucleic acid levels, promoter activity, and secretionin the rat. Endocrinology, 142(4), 1442–1447. https://doi.org/10.1210/endo.142.4.8069

  26. Morimoto, S., Mendoza-Rodríguez, C. A., Hiriart, M., Larrieta,M. E., Vital, P. & Cerbón, M. A. (2005). Protective effectof testosterone on early apoptotic damage induced bystreptozotocin in rat pancreas. The Journal of Endocrinology,187(2), 217–224. https://doi.org/10.1677/joe.1.06357

  27. Navarro, G., Allard, C., Morford, J. J., Xu, W., Liu, S., Molinas,A. J., Butcher, S. M., Fine, N. H., Blandino-Rosano, M.,Sure, V. N., Yu, S., Zhang, R., Münzberg, H., Jacobson,D. A., Katakam, P. V., Hodson, D. J., Bernal-Mizrachi, E.,Zsombok, A. & Mauvais-Jarvis, F. (2018). Androgen excessin pancreatic β cells and neurons predisposes female miceto type 2 diabetes. JCI Insight, 3(12), e98607. https://doi.org/10.1172/jci.insight.98607

  28. Paik, S. G., Michelis, M. A., Kim, Y. T. & Shin, S. (1982).Induction of insulin-dependent diabetes by streptozotocin.Inhibition by estrogens and potentiation by androgens.Diabetes, 31(8 Pt 1), 724–729. https://doi.org/10.2337/diab.31.8.724

  29. Palomar-Morales, M., Morimoto, S., Mendoza-Rodríguez,C. A. & Cerbón, M. A. (2010). The protective effect oftestosterone on streptozotocin-induced apoptosis in betacells is sex specific. Pancreas, 39(2), 193–200. https://doi.org/10.1097/MPA.0b013e3181c156d9

  30. Pang, S. T., Dillner, K., Wu, X., Pousette, A., Norstedt, G.& Flores-Morales, A. (2002). Gene expression profilingof androgen deficiency predicts a pathway of prostateapoptosis that involves genes related to oxidativestress. Endocrinology, 143(12), 4897–4906. https://doi.org/10.1210/en.2002-220327

  31. Parasuraman, S., Raveendran, R. & Kesavan, R. (2010). Bloodsample collection in small laboratory animals. Journal ofPharmacology & Pharmacotherapeutics, 1(2), 87–93.https://doi.org/10.4103/0976-500X.72350

  32. Pousette A. (1976). Demonstration of an androgen receptor inrat pancreas. The Biochemical Journal, 157(1), 229–232.https://doi.org/10.1042/bj1570229

  33. Rao, P. M., Kelly, D. M. & Jones, T. H. (2013). Testosterone andinsulin resistance in the metabolic syndrome and T2DMin men. Nature Reviews. Endocrinology, 9(8), 479–493.https://doi.org/10.1038/nrendo.2013.122

  34. Ritschl, L. M., Fichter, A. M., Häberle, S., von Bomhard, A.,Mitchell, D. A., Wolff, K. D. & Mücke, T. (2015). Ketamine-Xylazine Anesthesia in Rats: Intraperitoneal versusIntravenous Administration Using a Microsurgical FemoralVein Access. Journal of Reconstructive Microsurgery,31(5), 343–347. https://doi.org/10.1055/s-0035-1546291

  35. Sadowska-Krępa, E., Kłapcińska, B., Jagsz, S., Nowara, A.,Szołtysek-Bołdys, I., Chalimoniuk, M., Langfort, J. &Chrapusta, S. J. (2017). High-dose testosterone enanthatesupplementation boosts oxidative stress, but exerts littleeffect on the antioxidant barrier in sedentary adolescent malerat liver. Pharmacological Reports: PR, 69(4), 673–678.https://doi.org/10.1016/j.pharep.2017.02.023

  36. Salazar-García, M. & Corona, J. C. (2021). The use of naturalcompounds as a strategy to counteract oxidative stress inanimal models of diabetes mellitus. International Journal ofMolecular Sciences, 22(13), 7009. https://doi.org/10.3390/ijms22137009

  37. Sasikumar, R., Jyoti Das, A. & Chandra Deka, S. (2021). Invitro cytoprotective activity of cyanidin 3-glucoside extractsfrom Haematocarpus validus pomace on streptozotocininduced oxidative damage in pancreatic β-cells. SaudiJournal of Biological Sciences, 28(9), 5338–5348. https://doi.org/10.1016/j.sjbs.2021.05.065

  38. Sies, H. & Jones, D. P. (2020). Reactive oxygen species (ROS)as pleiotropic physiological signalling agents. Naturereviews. Molecular Cell Biology, 21(7), 363–383. https://doi.org/10.1038/s41580-020-0230-3

  39. Son, S. W., Lee, J. S., Kim, H. G., Kim, D. W., Ahn, Y. C. &Son, C. G. (2016). Testosterone depletion increases thesusceptibility of brain tissue to oxidative damage in arestraint stress mouse model. Journal of Neurochemistry,136(1), 106–117. https://doi.org/10.1111/jnc.13371

  40. Wang, N., Yi, W. J., Tan, L., Zhang, J. H., Xu, J., Chen, Y.,Qin, M., Yu, S., Guan, J. & Zhang, R. (2017). Apigeninattenuates streptozotocin-induced pancreatic β cell damageby its protective effects on cellular antioxidant defense. Invitro Cellular & Developmental Biology. Animal, 53(6),554–563. https://doi.org/10.1007/s11626-017-0135-4

  41. Xu, W., Niu, T., Xu, B., Navarro, G., Schipma, M. J. &Mauvais-Jarvis, F. (2017). Androgen receptor-deficientislet β-cells exhibit alteration in genetic markers ofinsulin secretion and inflammation. A transcriptomeanalysis in the male mouse. Journal of Diabetes and itsComplications, 31(5), 787–795. https://doi.org/10.1016/j.jdiacomp.2017.03.002

  42. Yao, Q. M., Wang, B., An, X. F., Zhang, J. A. & Ding, L.(2018). Testosterone level and risk of type 2 diabetes inmen: a systematic review and meta-analysis. EndocrineConnections, 7(1), 220–231. https://doi.org/10.1530/EC-17-0253

  43. Yaribeygi, H., Sathyapalan, T., Atkin, S. L. & Sahebkar,A. (2020). Molecular Mechanisms Linking OxidativeStress and Diabetes Mellitus. Oxidative Medicineand Cellular Longevity, 2020, 8609213. https://doi.org/10.1155/2020/8609213

  44. Zhang, Y., Mei, H., Shan, W., Shi, L., Chang, X., Zhu, Y.,Chen, F. & Han, X. (2016). Lentinan protects pancreaticβ cells from STZ-induced damage. Journal of Cellularand Molecular Medicine, 20(10), 1803–1812. https://doi.org/10.1111/jcmm.12865

  45. Zatroch, K. K., Knight, C. G., Reimer, J. N. & Pang, D. S.(2017). Refinement of intraperitoneal injection of sodiumpentobarbital for euthanasia in laboratory rats (Rattusnorvegicus). BMC Veterinary Research, 13(1), 60. https://doi.org/10.1186/s12917-017-0982-y




2020     |     www.medigraphic.com