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Cellular changes in the prostatic stroma of glucocorticoid-treated rats

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Abstract

Glucocorticoid hormones (GCs) have been widely used for the treatment of prostate cancer because of their inhibitory property against tumour growth. However, their mechanism of action in the prostate has received little attention. Excess GCs can lead to peripheral insulin resistance resulting in hyperglycaemia and hyperinsulinaemia. Insulin plays an important role as a cellular stimulant and high levels are related to low levels of androgens. Our objective has been to describe the effects of insulin resistance induced by dexamethasone treatment on the morphology of rat ventral prostate. Male adult Wistar rats received daily intraperitoneal injections of dexamethasone or saline for five consecutive days after which the rats were killed and the ventral prostate was removed, weighed and prepared for conventional and transmission electron microscopy (TEM). Dexamethasone treatment resulted in atrophy and decreased proliferative activity of prostatic epithelial cells. TEM analysis revealed changes in the epithelium-stroma interface, with some interruptions in the basement membrane. Fibroblasts showed a secretory phenotype with dilated endoplasmic reticulum. Smooth muscle cells exhibited a contractile pattern with 50% atrophy, an irregular membrane and twisted nuclei. Mitochondrial alterations, such as enlarged size and high electron density in the mitochondrial matrix, were also detected in smooth muscle cells. Insulin resistance induced by dexamethasone is thus associated with epithelial atrophy similar to that described for diabetic rats. However, GCs are responsible for morphological changes in the stromal cell population suggesting the activation of fibroblasts and atrophy of the smooth muscle cells.

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References

  • Albrecht M (2002) Effects of dexamethasone on proliferation and fibronectin synthesis by human primary prostatic stromal cells in vitro. Andrologia 34:11–21

    Article  PubMed  CAS  Google Scholar 

  • Andrews RC, Walker BR (1999) Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci 96:513–523

    Article  PubMed  CAS  Google Scholar 

  • Barbera M, Fierabracci V, Novelli M, Bombara M, Masiello P, Bergamini E, De Tata V (2001) Dexamethasone-induced insulin resistance and pancreatic adaptative response in ageing rats are not modified by oral vanadyl sulfate treatment. Eur J Endocrinol 145:799–806

    Article  PubMed  CAS  Google Scholar 

  • Barnard RJ, Aronson WJ, Tymchuk CN, Ngo TH (2002) Prostate cancer: another aspect of the insulin resistance syndrome? Obesity Rev 3:303–308

    Article  CAS  Google Scholar 

  • Bodker A, Bruuen J, Balslev A, Iversen HG, Meyhoff HH, Anderson KE (1999) Estrogen receptor in the human prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. Scand J Urol Nphrol 33:237–242

    Article  CAS  Google Scholar 

  • Cagnon VHA, Camargo AM, Rosa RM, Fabiani CR, Padovani CR, Martinez FE (2000) Ultrastructure study of the ventral lobe of the prostate of mice with streptozotocin induced diabetes (C57bl/6j). Tissue Cell 32:275–283

    Article  PubMed  CAS  Google Scholar 

  • Caldefie-Chazet F (2001) Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats. Metabolism 50:1054–1058

    Article  Google Scholar 

  • Carvalho CAF, Camargo AM, Cagnon VHA, Padovani CR (2003) Effects of experimental diabetes on the structure and ultrastructure of the coagulating gland of C57BL/6j and NOD mice. Anat Rec 270A:129–136

    Article  Google Scholar 

  • Castro M, Elias LLK (2003) Simpósio: urgências e emergências endócrinas, metabólicas e nutricionais. Capítulo II 36:375–379

    Google Scholar 

  • Cleutjens CBJM (1997) Both androgen receptor and glucocorticoid receptor are able to induce prostate-specific antigen expression, but differ in their growth-stimulating properties of LNCaP cells. Endocrinology 138:5293–5300

    Article  PubMed  CAS  Google Scholar 

  • Cotta-Pereira G, Rodrigo FG, David-Ferreira JF (1976) The use of tannic acid-glutaraldehyde in the study of elastic and elastic-related fibers. Stain Technol 51:7–11

    PubMed  CAS  Google Scholar 

  • Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1–10

    Article  PubMed  CAS  Google Scholar 

  • Duclos M, Gouarne C, Martin C, Rocher C, Pierre M, Letellier T (2004) Effects of corticosterone on muscle mitochondria identifying different sensitivity to glucocorticoids in Lewis and Fischer rats. Am J Physiol Endocrinol Metab 286:159–167

    Article  Google Scholar 

  • Durant S, Duval D, Homo-Delarche F (1986) Factors involved in the control of fibroblast proliferation by glucocorticoids: a review. Endocr Rev 7:254–269

    Article  PubMed  CAS  Google Scholar 

  • Goes RM, Zanetoni C, Tomisso TC, Ribeiro DL, Taboga SR (2007) Surgical and chemical castration induce differential histological response in prostate lobes of Mongolian gerbil. Micron 38:231–236

    Article  PubMed  CAS  Google Scholar 

  • Hayward SW, Cunha GR (2000) The prostate: development and physiology. Radiol Clin N Am 38:1–14

    Article  PubMed  CAS  Google Scholar 

  • Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948

    Article  PubMed  CAS  Google Scholar 

  • Jeong IK, Oh SH, Kim BJ, Chung JH, Min YK, Lee MS, Lee MK, Kim KW (2001) The effects of dexamethasone on insulin release and biosynthesis are dependent on the dose and duration of treatment. Diabetes Res Clin Pract 51:163–171

    Article  PubMed  CAS  Google Scholar 

  • Kapoor D, Malkin CJ, Channer KS, Jones TH (2005) Androgens, insulin resistance and vascular disease in men. Clin Endocrinol 63:239–250

    Article  CAS  Google Scholar 

  • Ling ZC, Khan A, Delauny F, Davani B, Ostenson CG, Gustafsson JA, Okret S, Landau BR, Efendic S (1998) Increased glucocorticoid sensitivity in islet beta-cells: effects on glucose 6-phosphatase, glucose cycling and insulin release. Diabetologia 41:634–639

    Article  PubMed  CAS  Google Scholar 

  • Lostroh AJ (1971) Effects of testosterone and insulin in vitro on maitenance and repair of the secretory epithelium of the mouse prostate. Endocrinology 88:500–503

    Article  PubMed  CAS  Google Scholar 

  • Manoli I, Lee H, Alesci S, Mcfann KK, Su YA, Kino T, Chrousos GP, Blackman MR (2005) Monoamine oxidase A is a major target gene for glucocorticoids in human skeletal muscle cells. FASEB J express article 10, published online DOI 10.1096/fj.04–3660fje

  • Mitsui T, Azuma H, Nagasawa M, Iuchi T, Akaike M, Odomi M, Matsumoto T (2002) Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle. J Neurol 249:1004–1009

    Article  PubMed  CAS  Google Scholar 

  • Porte D Jr (1999) Mechanisms for hyperglycemia in the metabolic syndrome. The key role of β cell disfunction. Ann N Y Acad Sci 892:73–83

    CAS  Google Scholar 

  • Psarra AMG, Solakidi S, Sekeris CE (2006) The mitochondria as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol 246:21–33

    Article  PubMed  CAS  Google Scholar 

  • Rafacho A, Roma LP, Taboga SR, Boschero AC, Bosqueiro JR (2007) Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets. Can J Physiol Pharmacol 85:536–545

    Article  PubMed  CAS  Google Scholar 

  • Reiter E, Hennuy B, Bruynix M, Cornet A, Klug M, McNamara M, Closset J, Hennen G (1999) Effects of pituitary hormones on the prostate. Prostate 38:159–165

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro DL, Caldeira EJ, Candido EM, Manzato AJ, Taboga SR, Cagnon VA (2006) Prostatic stromal microenvironment and experimental diabetes. Eur J Histochem 50:51–60

    PubMed  CAS  Google Scholar 

  • Ross RW, Kantoff PW (2007) Predicting outcomes in prostate cancer: how many more nomograms do we need? J Clin Oncol 25:3563–3564

    Article  PubMed  Google Scholar 

  • Ruzzin J, Wagman AS, Jensen J (2005) Glucocorticoid-induced insulin resistance in skeletal mucles: defects in insulin signaling and the effects of a selective glycogen sythase kinase-3 inhibitor. Diabetologia 48:2119–2130

    Article  PubMed  CAS  Google Scholar 

  • Saad MJ, Folli F, Kahn JA, Kahn CR (1993) Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. J Clin Invest 92:2065–2072

    Article  PubMed  CAS  Google Scholar 

  • Saika T, Kusaka N, Tsushima T, Yamato T, Ohashi T, Suyama B, Arata B, Nasu Y, Kumun H (2001) Treatment of androgen-independent prostate cancer with dexamethasone: a prospective study in stage D2 patients. Int J Urol 8:290–294

    Article  PubMed  CAS  Google Scholar 

  • Santos CL, Rafacho A, Bosqueiro JR (2007) Efeitos da administração de dexametasona in vivo sobre a glicemia, insulinemia e substratos circulantes são dependentes do tempo de tratamento. Biosci J 23:101–110

    Google Scholar 

  • Scarano WR, Cordeiro RS, Goes RM, Carvalho HF, Taboga SR (2004) Tissue remodeling in guinea pig lateral prostate at different ages after estradiol treatment. Cell Biol Int 29:778–784

    Article  CAS  Google Scholar 

  • Scott AM, Atwater I, Rojas E (1981) A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia 21:470–475

    Article  PubMed  CAS  Google Scholar 

  • Vilamaior PSL, Felisbino SL, Taboga SR, Carvalho HF (2000) Collagen fiber reorganization in the rat ventral prostate following androgen deprivation: a possible role for the smooth muscle cells. Prostate 45:253–258

    Article  PubMed  CAS  Google Scholar 

  • Weibel ER (1963) Principles and methods for the morphometric study of the lung and other organs. Lab Invest 12:131–155

    PubMed  CAS  Google Scholar 

  • Wood SC, Lotter EC, McKay LD (1979) Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282:503–505

    Article  Google Scholar 

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Acknowledgments

The authors express their gratitute to Mr. Luis Roberto Faleiros Jr. for his technical support.

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Correspondence to R. M. Góes.

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This work formed a part of the doctoral thesis of D.L. Ribeiro and was supported by CAPES (Coordinating Body for Training), CNPq (Brazilian National Research and Development Council), and FAPESP (State of São Paulo Research Foundation).

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Ribeiro, D.L., Rafacho, A., Bosqueiro, J.R. et al. Cellular changes in the prostatic stroma of glucocorticoid-treated rats. Cell Tissue Res 332, 499–508 (2008). https://doi.org/10.1007/s00441-008-0581-0

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  • DOI: https://doi.org/10.1007/s00441-008-0581-0

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