title: Prostate hyperplasia caused by long-term obesity is characterized by high deposition of extracellular matrix and increased content of MMP-9 and VEGF.
abstract: Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long-term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high-fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α-actin, vimentin, chondroitin sulphate and metalloproteinases (MMP-2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione-S-Transferase (GST) were quantified by enzymatic assay. Long-term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α-actin and MMP-9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long-term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.
authors.affiliation: Histology Sector, Institute of Biomedical Sciences, Federal University of Uberlândia- UFU, Uberlândia, MG, Brazil.
authors.forename: Silas Amâncio
authors.initials: SA
authors.lastname: Silva
authors.forename: Marina Guimarães
authors.initials: MG
authors.lastname: Gobbo
authors.forename: Maria Etelvina
authors.initials: ME
authors.lastname: Pinto-Fochi
authors.forename: Alex
authors.initials: A
authors.lastname: Rafacho
authors.forename: Sebastião Roberto
authors.initials: SR
authors.lastname: Taboga
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: Almeida
authors.forename: Rejane Maira
authors.initials: RM
authors.lastname: Góes
authors.forename: Daniele Lisboa
authors.initials: DL
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009765:Obesity / Q000150:complications*; D010084:Oxidation-Reduction; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000097:blood / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D012307:Risk Factors; D017154:Stromal Cells / Q000201:enzymology* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D011944:Receptors, Androgen; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013739:Testosterone; D008315:Malondialdehyde; D002374:Catalase; D005982:Glutathione Transferase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: MMP-9; androgen receptor; hyperplasia; obesity; prostate; stromal remodelling