Steroid Hormone Receptors, Matrix Metalloproteinases, Insulin-Like Growth Factor, and Dystroglycans Interactions in Prostatic Diseases in the Elderly Men A.C. HETZL, 1 W.J. FA ´ VARO, 1 A. BILLIS, 2 U. FERREIRA, 3 AND V.H.A. CAGNON 1 * 1 Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil 2 Department of Pathology, School of Medicine, State University of Campinas (UNICAMP), Campinas, SP, Brazil 3 Department of Urology, School of Medicine, State University of Campinas (UNICAMP), Campinas, SP, Brazil KEY WORDS prostatic diseases; steroid hormones; insulin-like growth factors; dystroglycans; matrix metalloproteinases; prostate; hormone interactions; aging; growth factors ABSTRACT OBJECTIVES: The aim of this study was to evaluate the reactivity of steroid hor- mone receptors (SHRs), dystroglycans (DGs), matrix metalloproteinases (MMPs), insulin-like growth factor receptor (IGFR-1), and laminin (Lam) in both prostatic stromal and epithelial com- partments showing different diseases in elderly men. METHODS: Sixty prostatic samples were obtained from 60- to 90-year-old patients (mean 63 years) with and without prostatic lesions from Hospital of the School of Medicine, State University of Campinas (UNICAMP). The Samples were divided into standard (no lesions); high grade prostatic intraepithelial neoplasia (HGPIN); pros- tatic cancer (PC); and benign prostatic hyperplasia (BPH) groups. The samples were submitted to immunohistochemistry and Western blotting analyses. Research Ethics Committee of the School of Medicine, University of Campinas/UNICAMP (number 0094.0.146.000-08). RESULTS: The results showed increased IGFR-1 and MMPs protein levels in the PC and HGPIN groups. Decreased aDG and bDG protein levels were verified in the PC and HGPIN groups. Androgen re- ceptor (AR) reactivity was similar among all groups. Estrogen receptor a (Era) immunoreactivity was more intense in the epithelium in the PC and HGPIN groups. Estrogen receptor b (ERb) im- munoreactivity was weak in the epithelium of the HGPIN and PC groups. CONCLUSIONS: To conclude, there was an association among IGFR-1, MMPs, and SHRs, indicating IGFR-1 as a tar- get molecule in prostate therapy, considering the IGF proliferative properties. Also, the distinct SHRs reactivities in the lesions in both prostatic compartments indicated different paracrine sig- nals and pointed out the importance of estrogenic pathways in the activation of these disorders. Microsc. Res. Tech. 00:000–000, 2012. V V C 2012 Wiley Periodicals, Inc. INTRODUCTION Senescence is a determining factor for prostatic disor- ders considering the occurrence of hormonal imbalance (Leav et al., 2001; Marcelli et al., 1999). The prostatic androgen dependence points out androgen as a crucial hormone to the maintenance of the morphogenesis, functional activity, proliferation, and differentiation of this organ (Cunha et al., 2002; Imamov et al., 2005). Testosterone and dihydrotestosterone are the main androgens that induce prostatic differentiation (Hsing et al., 2002; Toorians et al., 2003). However, the pros- tate is sensitive to other hormones which act in associ- ation with the androgens, influencing not only normal prostatic function but also pathological processes (Cunha et al., 2002; Weihua et al., 2001). Estrogens have antiandrogen effects and negatively regulate the hypothalamus-pituitary-gonadal axis, thereby reduc- ing androgen production by Leydig cells in adult rodents (Weihua et al., 2002). Proteins such as insulin-like growth factor (IGF) are important mitogenic factors for maintaining prostatic function (Djavan et al., 2001). IGFs are produced by pros- tatic stromal cells and act as paracrine growth factors in the glandular epithelium via transmembrane receptors (Djavan et al., 2001). IGFs overexpression may be an im- portant factor in stimulating cancer cell proliferation and metastasis in the prostate (Denley et al., 2005). Clin- ical and epidemiological studies demonstrated that increased IGF-1 serum level is a potent risk factor for the development of benign hyperplasia and prostatic car- cinogenesis (Djavan et al., 2001; Pavelic et al., 2007). According to the Rowlands et al. (2012), the IGF-I and IGFBP3 levels and the relation to advanced prostate can- cer could influence the invasiveness of set cancers. Dystroglycan is a major nonintegrin adhesion mole- cule expressed in a wide variety of tissues at the inter- *Correspondence to: Vale ´ria H.A. Cagnon, PhD, Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), P.O. Box 6109, 13083-865 Campinas, SP, Brazil. E-mail: Received 14 December 2011; accepted in revised form 13 March 2012 Contract grant sponsor: Sa ˜ o Paulo Research Foundation; Contract grant numbers: 2008/53468-1, 2009/50396-2 DOI 10.1002/jemt.22049 Published online in Wiley Online Library (wileyonlinelibrary.com). V V C 2012 WILEY PERIODICALS, INC. MICROSCOPY RESEARCH AND TECHNIQUE 00:000–000 (2012)