Abstract
Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies.
Highlights
Benign prostatic hyperplasia (BPH) is a common disease in middle and old aged men and may significantly affect the quality of life[1, 2]
BPH is associated with voiding and storage lower urinary tract symptoms (LUTS) which reduce the life quality of the patients
Α1-AR antagonists are considered one of the first-line therapies to reduce LUTS associated with clinical BPH with proven efficacy [22,23,24]
Summary
Benign prostatic hyperplasia (BPH) is a common disease in middle and old aged men and may significantly affect the quality of life[1, 2]. Androgen receptor, insulin-like growth factor-1 and a number of other growth hormones have been found to play roles in BPH[18] These models are typically used to test drugs that can prevent hyperplasia or reduce the size of the prostate. For α1-AR antagonists, their main therapeutic effect is to easy the voiding or obstructive symptoms caused by enlarged prostate Their in vivo efficacies were commonly evaluated in rat bladder outlet obstruction (BOO) model established by partial ligature of the proximal urethra[19]. We would like to see whether young adult male dogs could be induced to develop BPH with hormone, and could this model be used to evaluate the effect of α1-AR antagonist
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