Influence of testosterone hormone therapy on prostate tissue remodeling in healthy adult rats: use of fractal analysis as a diagnostic method

Authors

DOI:

https://doi.org/10.33448/rsd-v11i7.29772

Keywords:

Prostate ; Testosterone; Fractals; Pathology.

Abstract

Testosterone therapy is often indicated for the treatment of several pathological conditions related to aging, including osteoporosis and metabolic syndrome. However, some questions persist about the safety of the use of the therapy, due to the increased susceptibility of non-prostatic disease. The histopathological analyzes are based on subjective methodologies, being important to the validation of quantitative methods, such as fractal analysis, to detect subtle morphological changes and transform the complexity of the structures into quantitative analytical data. Therefore, the study investigated the effects of testosterone therapy on the prostatic microenvironment remodeling and the validation of an effective method for tissue analysis. Wistar rats with 150 days olde were divided into two experimental groups (n = 5): Group T: received subcutaneous injections of testosterone cypionate (5mg/kg body weight) diluted in corn oil every other day for 4 weeks; Group C: received subcutaneous injections of corn oil as vehicle. The animals were euthanized at 180 days old, in a CO2 chamber, followed by decapitation. After euthanasia, the ventral prostate was collected, dissected and histologically processed to perform the fractal, stereological and epithelial height analysis. There was a reduction in the fractal dimension in group T, accompanied by an increase in epithelial height. Stereological analysis revealed a decrease in the stromal compartment and an increase in the epithelial compartment. Likewise, the results demonstrate that the fractal analysis was effective in assessing alterations related to hormonal supplementation with testosterone, evidencing prostatic morphological alterations observed in the other methods.

Author Biographies

Izabella Tossato Abonizio, Universidade do Oeste Paulista

Faculdadede Ciências da Saúde

Sarah Raquel César Dourado, Universidade do Oeste Paulista

Faculdade de Ciências da Saúde

Thainá Cavalleri Sousa, Universidade do Oeste Paulista

Programa de Pós-Graduação em Ciência Animal

Maria Luiza Silva Ricardo, Universidade do Oeste Paulista

Programa de Pós-Graduação em Ciência Animal

Wilmer Ramírez-Carmona, Universidade Estadual Paulista

Departamento de Odontologia Restauradora

Leonardo de Oliveira Mendes, Universidade do Oeste Paulista

Mestrado em CIências da Saúde

Programa de Pós-Graduação em Ciência Animal

References

Ahmad, I., Sansom, O. J., & Leung, H. Y. (2008) Advances in mouse models of prostate cancer. Expert Reviews in Molecular Medicine, 10(16). doi: http://doi.org/10.1017/S1462399408000689.

Assis, T. A., Miranda, J. G. V., Mota, F. B., Andrade, R. F. S., & Castilho, C. M. C. (2008) Geometria fractal: propriedades e características de fractais ideais. Revista Brasileira de Ensino de Física, 30(2)2304.1-2304.10. doi: https://doi.org/10.1590/S1806-11172008000200005.

Bizzarri, M. Giuliani, A., Cucina, A., Anselmi F. D., Soto, A. M., & Sonnenschein, C. (2011) Fractal analysis in a systems biology approach to cancer. Semin Cancer Biol, 21(3), 175-182, doi: 10.1016 / j.semcancer.2011.04.002.

Cunha, G. R., Hayward, S. W., Dahiya, R., & Foster, B. A. (1996). Smooth muscle-epithelial interactions in normal and neoplastic prostatic development. Acta anatomica, 155(1), 63–72. doi: https://doi.org/10.1159/000147791.

de Arruda, P. F., Gatti, M., Facio, F. N. Jr., de Arruda, J. G., Moreira, R. D., Murta, L. O. Jr., de Arruda, L. F., & de Godoy, M. F. (2013). Quantification of fractal dimension and Shannon's entropy in histological diagnosis of prostate cancer. BMC clinical pathology, 13(6). Doi: https://doi.org/10.1186/1472-6890-13-6.

Deckardt, K., Weber, I., Kaspers, U., Hellwig, J., Tennekes, H., & van Ravenzwaay, B. (2007). The effects of inhalation anaesthetics on common clinical pathology parameters in laboratory rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 45(9), 1709–1718. https://doi.org/10.1016/j.fct.2007.03.005.

Drewa, T., & Chlosta, P. (2010). Testosterone supplementation and prostate cancer, crontroversis still exist. Acta Poloniae Pharmaceutica - Drug Research, 67(5),543-546. Recuperado de https://pubmed.ncbi.nlm.nih.gov/20873424/.

Ferro, D. P., Falconi, M. A., Adam, R. L., Ortega, M. M., Lima, C. P., de Souza, C. A., Lorand-Metze, I., & Metze, K. (2011) Fractal characteristics of May-Grünwald-Giemsa stained chromatin are independent prognostic factors for survival in multiple myeloma. PLoS One, 6(6),e20706. doi: 10.1371 / journal.pone.0020706.

Frisch, K. E., Duenwald-Kuehl, S. E., Lakes, R. S., & Vanderby, R. Jr. (2012). Quantification of collagen organization using fractal dimensions and Fourier transforms. Acta Histochemica, 114(2)140-144. doi: https://doi.org/10.1016/j.acthis.2011.03.010

Gheonea, D. I., Streba, C. T., Vere, C. C., Şerbănescu, M., Pirici, D., Comănescu, M., Streba, L. A., Ciurea, M. E., Mogoantă, S., & Rogoveanu, I. (2014). Diagnosis system for hepatocellular carcinoma based on fractal dimension of morphometric elements integrated in an artificial neural network. BioMed research international, 2014, 239706. https://doi.org/10.1155/2014/239706.

Giltay, E. J., Tishova, Y. A., Mskhalaya, G. J., Gooren, L. J., Saad, F., & Kalinchenko, S. Y. (2010). Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. The journal of sexual medicine, 7(7),2572–2582. doi:https://doi.org/10.1111/j.1743-6109.2010.01859.x.

Gooren, L. J., Behre, H. M., Saad, F., Frank, A., & Schwerdt, S. (2007). Diagnosing and treating testosterone deficiency in different parts of the world. Results from global market research. The aging male : the official journal of the International Society for the Study of the Aging Male, 10(4),173–181. doi: https://doi.org/10.1080/13685530701600885.

Gross, S. A., & Didio, L. J. (1987). Comparative morphology of the prostate in adult male and female Praomys (Mastomys) Natalensis studied with electron microscopy. Journal of submicroscopic cytology, 19(1),77–84. Recuperado de: https://pubmed.ncbi.nlm.nih.gov/3560297/

Gudea, A. I., & Stefan, A. C. (2013). Histomorphometric, fractal and lacunarity comparative analysis of sheep (Ovis aries), goat (Capra hircus) and roe deer (Capreolus capreolus) compact bone samples. Folia morphologica, 72(3), 239–248. doi: https://doi.org/10.5603/fm.2013.0039

Hall, J. E. (2011). Guyton & Hall: Tratado de Fisiologia Médica. (12 ed.) Filadélfia: Elsevier.

Hermoso, D. A. M. Bizerra, P. F. V., Constantin, R. P., Ishi-Iwamoto, E. L., Gilglioni, E. H. (2020). Association between metabolic syndrome, steatosis, and testosterone deficiency: evidences from studies with men and rodents. Aging Male, 23(5), 1296-1315. doi: 10.1080/13685538.2020.1764927.

Jesik, C. J., Holland, J. M., & Lee, C. (1982). An anatomic and histologic study of the rat prostate. The Prostate, 3(1)81-97. doi: 10.1002/pros.2990030111.

Kapoor, D., Goodwin, E., Channer, K. S., & Jones, T. H. (2006). Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.European journal of endocrinology, 154(6), 899–906. doi: https://doi.org/10.1530/eje.1.02166.

Karperien, A., Jelinek, H. F., Leandro, J. J., Soares, J. V., Cesar, R. M., Jr, & Luckie, A. (2008). Automated detection of proliferative retinopathy in clinical practice. Clinical ophthalmology (Auckland, N.Z.), 2(1),109–122. doi: https://doi.org/10.2147/opth.s1579.

Kelly, D. M., & Jones, T. H. (2013). Testosterone: a metabolic hormone in health and disease. The Journal of endocrinology, 217(3),R25–R45. doi: https://doi.org/10.1530/JOE-12-0455.

Kurita, T., Medina, R. T., Mills, A. A., & Cunha, G. R. (2004). Role of p63 and basal cells in the prostate. Development (Cambridge, England), 131(20),4955–4964. doi: https://doi.org/10.1242/dev.01384.

Labat-Robert, J., Bihari-Varga, M., & Robert, L. (1990). Extracellular matrix. FEBS letters, 268(2),386–393. doi: https://doi.org/10.1016/0014-5793(90)81291-u.

Lenfant, L., Leon, P., Cancel-Tassin, G., Audouin, M., Staerman, F., Rouprêt, M., Cussenot, O. (2020). Testosterone replacement therapy (TRT) and prostate cancer: An uptade systematic review with a focus on previous or active localized prostate cancer. Urol Oncol 38(8), 661-670. doi: 10.1016/j.urolonc.2020.04.008.

Marchiani, S., Tamburrino, L., Nesi, G., Paglierani, M., Gelmini, S., Orlando, C., Maggi, M., Forti, G., & Baldi, E. (2010). Androgen-responsive and -unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation. International journal of andrology, 33(6),784–793. doi: https://doi.org/10.1111/j.1365-2605.2009.01030.x.

Marker, P. C., Donjacour, A. A., Dahiya, R., & Cunha, G. R. (2003). Hormonal, cellular, and molecular control of prostatic development. Developmental biology, 253(2), 165–174. doi: https://doi.org/10.1016/s0012-1606(02)00031-3.

Marks, L. S., Mazer, N. A., Mostaghel, E., Hess, D. L., Dorey, F. J., Epstein, J. I., Veltri, R. W., Makarov, D. V., Partin, A. W., Bostwick, D. G., Macairan, M. L., & Nelson, P. S. (2006). Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA, 296(19),2351–2361. doi: https://doi.org/10.1001/jama.296.19.2351.

Mendes, L. O., Castilho, A., Pinho, C. F., Gonçalvez, B. F., Razza, E. M., Chuffa, L., Anselmo-Franci, J. A., Scarano, W. R., & Martinez, F. E. (2018). Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats. Cell biology international, 42(9),1200–1211. doi: https://doi.org/10.1002/cbin.10990.

Metze K. (2013). Fractal dimension of chromatin: potential molecular diagnostic applications for cancer prognosis. Expert review of molecular diagnostics, 13(7),719–735. doi: https://doi.org/10.1586/14737159.2013.828889.

Morgentaler A. (2009). Testosterone therapy in men with prostate cancer: scientific and ethical considerations. The Journal of urology, 181(3),972–979. doi: https://doi.org/10.1016/j.juro.2008.11.031.

Narbaitz R. (1975). Embryology, anatomy and histology of the male sex accessory glands. In: D. Brandes (Ed.). Male sex accessory organs (p. 3-15). New York: Academic Press.

Nazian, S. J. (1988). Serum concentrations of reproductive hormones after administration of various anesthetics to immature and young adult male rats. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 187(4),482–487. doi: https://doi.org/10.3181/00379727-187-42692.

Nicholson, T. M., & Ricke, W. A. (2011). Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation; research in biological diversity, 82(4-5),184–199. doi: https://doi.org/10.1016/j.diff.2011.04.006.

Pacagnelli, F. L., Sabela, A. K. D. A., Mariano, T. B., Ozaki, G. A. T., Castoldi, R. C., Carmo, E. M., Carvalho, R. F., Tomasi, L. C., Okoshi, K., & Vanderlei, C. M. (2016). Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats. Arquivo Brasileiro de Cardiologia. 107(1)33-39. doi: http://dx.doi.org/10.5935/abc.20160083.

Pajevic, M., Aleksic, M., Golic, I., Markelic, M., Otasevic, V., Jankovic, A., Stancic, A., Korac, B., & Korac, A. (2018). Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling. Folia morphologica, 77(3),478–484. doi: https://doi.org/10.5603/FM.a2017.0106.

Price, D. (1963). Comparative aspects of development and structure in the prostate. National Cancer Institute monograph, 12,1–27. Recuperado de:https://pubmed.ncbi.nlm.nih.gov/14072991/.

Pu, Y., Wang, W., Al-Rubaiee, M., Gayen, S. K., & Xu, M. (2012). Determination of optical coefficients and fractal dimensional parameters of cancerous and normal prostate tissues. Applied spectroscopy, 66(7),828–834. do:i https://doi.org/10.1366/11-06471.

Reyes-Vallejo, L., Lazarou, S., & Morgentaler, A. (2007). Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone. The journal of sexual medicine, 4(6),1757–1762. doi: https://doi.org/10.1111/j.1743-6109.2006.00381.x.

Rodrigues, R. M. C. (2016). A análise fractal como ferramenta de prognóstico para o sucesso implantar – uma revisão do estado da arte. Portugal: Faculdade de Medicina Dentária da Universidade do Porto.

Salam, R., Kshetrimayum, A. S., & Keisam, R. (2012). Testosterone and metabolic syndrome: The link. Indian journal of endocrinology and metabolism, 16 Suppl 1(Suppl1),S12–S19. doi: https://doi.org/10.4103/2230-8210.94248.

Sáttolo, S., Carvalho, C. A., & Cagnon, V. H. (2004). Influence of hormonal replacement on the ventral lobe of the prostate of rats (Rattus norvegicus albinus) submitted to chronic ethanol treatment. Tissue & cell, 36(6), 417–430. doi: https://doi.org/10.1016/j.tice.2004.07.004.

Scarano, W. R., Vilamaior, P. S., & Taboga, S. R. (2006). Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology, 288(11),1190–1200. doi: https://doi.org/10.1002/ar.a.20391.

Scarano, W. R. (2002). Efeito do estradiol sobre a próstata da cobaia Cavia porcellus em diferentes fases do desenvolvimento pós-natal. (Dissertação de Mestrado). Universidade Estadual de Campinas, Instituto de Biologia - UNICAMP. Campinas – SP.

Shoskes, J. J., Wilson, M. K., & Spinner, M. L. (2016). Pharmacology of testosterone replacement therapy preparations. Translational andrology and urology, 5(6),834–843. doi: https://doi.org/10.21037/tau.2016.07.10.

Silverthorn, D. U. (2010). Fisiologia Humana: Uma abordagem integrada. (5-ed.). Brasil: ARTMED.

Souza, G. R. (2015). Estudo do potencial migratório de células tumorais prostáticas expostas à fibronectina. (Dissertação de Mestrado). Universidade Estadual Paulista “Júlio de Mesquita Filho”- UNESP, Botucatu, SP.

Sugimura, Y., Cunha, G. R., & Donjacour, A. A. (1986). Morphogenesis of ductal networks in the mouse prostate. Biology of reproduction, 34(5),961–971. doi: https://doi.org/10.1095/biolreprod34.5.961.

Timms, B. G., Howdeshell, K. L., Barton, L., Bradley, S., Richter, C. A., & vom Saal, F. S. (2005). Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. Proceedings of the National Academy of Sciences of the United States of America, 102(19),7014–7019. doi: https://doi.org/10.1073/pnas.0502544102.

Tuxhorn, J. A., Ayala, G. E., & Rowley, D. R. (2001). Reactive stroma in prostate cancer progression. The Journal of urology, 166(6),2472–2483. Recuperado de: https://pubmed.ncbi.nlm.nih.gov/11696814/.

Waliszewski P. (2016). The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas. Frontiers in physiology, 7, 34. doi: https://doi.org/10.3389/fphys.2016.00034.

Waliszewski, P., Wagenlehner, F., Gattenlöhner, S., & Weidner, W. (2015). On the relationship between tumor structure and complexity of the spatial distribution of cancer cell nuclei: a fractal geometrical model of prostate carcinoma. The Prostate, 75(4),399–414. doi: https://doi.org/10.1002/pros.22926.

West B. J. (2010). Fractal physiology and the fractional calculus: a perspective. Frontiers in physiology, 1, 12. doi: https://doi.org/10.3389/fphys.2010.00012.

World Health Organization. (2009). Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. Geneva, Suiça.

Yassin, A. A., & Saad, F. (2013). Testosterone and obesity: generic aspacts and specific experience. The Journal of Men's Health and Gender, 4(3)372-373.

Published

29/05/2022

How to Cite

ABONIZIO, I. T.; DOURADO, S. R. C.; SOUSA, T. C.; RICARDO, M. L. S.; RAMÍREZ-CARMONA, W. .; MENDES, L. de O. . Influence of testosterone hormone therapy on prostate tissue remodeling in healthy adult rats: use of fractal analysis as a diagnostic method. Research, Society and Development, [S. l.], v. 11, n. 7, p. e39811729772, 2022. DOI: 10.33448/rsd-v11i7.29772. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/29772. Acesso em: 19 apr. 2024.

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Section

Health Sciences