Tohoku J. Exp. Med., 2012, 226(2)

Androgen Deprivation Induces Bladder Histological Abnormalities and Dysfunction via TGF-β in Orchiectomized Mature Rats

YONG ZHANG,¹ JIMIN CHEN,¹ LINYI HU¹ and ZHAODIAN CHEN¹

¹Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Symptomatic late-onset hypogonadism, one of the most common elder diseases, is defined as a syndrome associated with a deficiency in serum testosterone. Recent studies have indicated that androgen deficiency in men is also associated with lower urinary tract symptoms and bladder dysfunction. To determine the pathologic consequences of androgen deprivation in bladder histology and function, we addressed the underlying mechanism. Male rats were divided into 4 groups: emasculated rats (EMR), emasculated rats treated with testosterone, emasculated rats treated with anti- transforming growth factor-β (TGF-β) neutralizing antibody, and sham surgery rats. TGF-β is a common profibrotic factor that mediates the pathologic process of fibrosis in multiple organs. Two months later, urodynamic evaluations were employed to determine the bladder function in vivo. And then rats were sacrificed, and the bladder tissues were collected. Histological studies were employed to determine the degree of bladder fibrosis. Real time PCR was used to evaluate the mRNA level of pro-collagen I, a fibrotic marker. We demonstrate here that androgen deficiency induces bladder fibrosis and decreases the bladder maximal volume and compliance. Androgen replacement treatment completely prevented the histological and functional abnormalities induced by androgen deficiency. Subsequently, we identified that androgen deprivation induced the induction of TGF-β mRNA level. Importantly, treatment with anti-TGF-β antibody abolished androgen deprivation-induced bladder fibrosis and dysfunction. Our study reveals an essential role of TGF-β in the pathogenesis of androgen deprivation-induced bladder fibrosis and dysfunction and offers a potential target for prevention and treatment of bladder dysfunction associated with androgen deficiency.

keywords —— androgen deprivation; androgen replacement treatment; bladder dysfunction; bladder fibrosis; transforming growth factor-β

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 226, 121-128

Correspondence: Zhaodian Chen, Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.

e-mail: zhaodianchen12@126.com