Alpha-blockade downregulates myosin heavy chain gene expression in human benign prostatic hyperplasia

Objectives. Smooth muscle (SM), a major component of prostate stroma, plays an important role in the pathogenesis of benign prostatic hyperplasia. In many muscle systems, steroid hormones and alpha,adrenergic neurotransmitter s tightly regulate expression of contractile proteins. In this study, SM co ntent and the expression of myosin heavy chain (MHC) in tissues from patien ts with benign prostatic hyperplasia treated with androgen ablation or alph a-blockade were compared with untreated controls. Methods. Prostatic periurethral tissue specimens from patients receiving lu teinizing hormone-releasing hormone analogues (n = 12), alpha-blocking agen ts (n = 12), and no treatment (n = 13) were examined. The samples were anal yzed for SM MHC mRNA expression using competitive reverse transcription-pol ymerase chain reaction. SM content was measured by morphometric analysis of trichrome-stained sections. Results. Stromal SM constituted 45.4% +/- 8.6%, 48.1% +/- 18.4%, and 45.9% +/- 10.8% of the total tissue in androgen ablated, alpha-blocked, and untre ated tissues, respectively. No significant difference was observed among th ese three groups (P = 0.84, analysis of variance). However, SM MHC mRNA exp ression was markedly decreased in the alpha-blockade group (0.15 +/- 0.02 a ttomole/mg tissue) compared with the androgen-ablated (0.58 +/- 0.15 attomo le/mg tissue) or control (0.44 +/- 0.10 attomole/mg tissue) groups. The rel ationship between SM content and expression of SM MHC significantly differe d among the groups (P = 0.02, analysis of variance). Conclusions. Androgen ablation and alpha-blockade do not appear to alter th e histologic characteristics of prostate stroma in men with symptomatic ben ign prostatic hyperplasia. However, contractile protein gene expression in stromal SM cells is significantly altered after alpha-blockade. These data suggest that, in addition to the simple relaxation of muscle tone, alpha-bl ocking agents may affect the phenotypic expression of contractile proteins in prostate SM cells. UROLOGY 57: 170-175, 2001. (C) 2001, Elsevier Science Inc.