Journal
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
Volume 226, Issue 2, Pages 121-128Publisher
TOHOKU UNIV MEDICAL PRESS
DOI: 10.1620/tjem.226.121
Keywords
androgen deprivation; androgen replacement treatment; bladder dysfunction; bladder fibrosis; transforming growth factor-beta
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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-beta (TGF-beta) neutralizing antibody, and sham surgery rats. TGF-beta 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-beta mRNA level. Importantly, treatment with anti-TGF-beta antibody abolished androgen deprivation-induced bladder fibrosis and dysfunction. Our study reveals an essential role of TGF-beta 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.
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