%0 Journal Article
%T Is Transforming Growth Factor-¦Â Signaling Activated in Human Hypertrophied Prostate Treated by 5-Alpha Reductase Inhibitor?
%A Hye Kyung Kim
%A Chen Zhao
%A Bo Ram Choi
%A Han Jung Chae
%A Do Sung Kim
%A Jong Kwan Park
%J Disease Markers
%D 2013
%R 10.1155/2013/783287
%X Background and Aim. It is well known that androgen deprivation relates to penile fibrosis, so we hypothesize that long-term treatment with 5-alphareductase inhibitors (5ARIs) may increase the risk of fibrosis of prostate. Patients and Methods. Thirty-two BPH patients who underwent transurethral resection of the prostate were enrolled. The patients were divided into two groups: group one, 16 patients underwent TURP who had been treated with tamsulosin for 2 years; group two, 16 patients underwent TURP who had been treated with combination of tamsulosin and dutasteride for at least 1 year. We evaluated the expressions of nNOS, iNOS, eNOS, TGF-¦Â1, TGF-¦Â2, phosphorylated-Smad2/3 (p-Smad2/3), E-cadherin, N-cadherin, and ¦Á-smooth muscle actin in the resected prostate tissues by western blotting, and the TGF-¦Â concentration was determined by ELISA kit. Results. The expressions of 3 isoforms of NOS were significantly increased in group 2 except of eNOS in lateral prostate, and the expressions of TGF-¦Â1, TGF-¦Â2, and p-Smad2/3 increased about 2-fold compared with group 1. In group 2, the E-cadherin expression decreased while N-cadherin expression increased significantly. Conclusions. The overexpression of nNOS may contribute to prostate smooth muscle relaxation; however, long-time treatment with 5£¿ARI increases the risk of fibrosis of prostate. 1. Introduction The 5-alpha reductase (5£¿AR) inhibitor (5£¿ARI) was developed to treat the patients with symptomatic benign prostatic hyperplasia (BPH) and decrease the frequency and risk of BPH-related morbidities [1, 2]. Presently available orally administered 5£¿ARIs, finasteride and dutasteride, inhibit 5£¿AR, an enzyme that catalyzes the irreversible reduction of testosterone (T) to dihydrotestosterone (DHT), with NADPH as the hydrogen donor [3]. Dutasteride is a selective inhibitor of 5£¿AR type 1 (5£¿AR1) and 5£¿AR type 2 (5£¿AR2). Finasteride is considered mainly an inhibitor of 5£¿AR2 and is approximately 50 times weaker in inhibiting 5£¿AR1 than 5£¿AR2 [4]. The development of BPH is an androgen-dependent process, and androgen suppression causes regression primarily of the epithelial elements of the prostate, resulting in a reduction in the size of the gland and improvement in symptoms [5, 6]. As we know, androgen deprivation by surgical or medical castration is associated with penile cavernosal fibrosis resulting in penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reductions in trabecular smooth muscle content, increases in deposition of extracellular matrix, and
%U http://www.hindawi.com/journals/dm/2013/783287/