Hypothesis / aims of study
Benign prostatic hyperplasia (BPH) is a common condition developping with age. Hormonal changes, particularly those affecting androgens, are thought to be the main cause. Other factors like metabolic symdrome, obesity, diabetes or cardiac diseases, contribute to BPH. The Tally Ho (TH) mouse is an established polygenic model of type 2 diabetes, with sustained hyperglycemia and insulin resistance at a very early age (8 weeks). The present project examines the characteristics of the prostate tissue in aging TH mice compared to its non-diabetic counterparts, the SWR mice.
Study design, materials and methods
Prostate tissues from TallyHo and SWR mice were harvested at 10, 14 and 18 weeks of age. Body weight, glycemia and prostate mass were measured. Prostate histology was examined using Masson’s trichrome. Contractile characteristics were assessed using organ bath. Proteins were semi-quantified by immunoblotting and data confirmed by immunofluorescence. Gene expression was evaluated by RT-qPCR.
Results
At age 18 weeks, Th mice were hyperglycemic (glycemia > 30mM) while SWR were normoglycemic. However, prostate weight were significantly lower in TH than SWR. Nonetheless, histology reveals massive epithelial hyperplasia at 18 weeks in TH, with luminal narrowing, increased muscle area and similar amount of collagen compared to SWR of the same age. Prostate piece contraction under electric stimulation (EFS) or carbachol (cholinergic agonist) were stronger in TH. There was no differences in CTGF, fibronectin, PSA, SMAD7, TGF-β, or TNF-α mRNA expression between groups. On the other hand, immunoblotting revealed decreased junction protein (occludin, E-cadherin and ZO-1) levels in TH, while reduced BAX and increased Bcl-2 indicate a shift toward pro-survival signaling. Surprinsingly, proteins involved in contraction (smoothelin and SMMHC-I) were decreased in TH while beta-actin was unaffected. Finally vimentin was increased but not cytokeratin 13. Immunofluorescence images confirmed the data obtained. No changes could be seen in inflammatory markers CD23, CD68 or TNF-α.
Interpretation of results
The TallyHo mouse develops epithelial prostatic hyperplasia, making it suitable to study structural changes happening during hyperglycemia. It does not mimick the inflammatory pattern of BPH, suggesting that androgens might rely on different pathways.