Korean J Androl.  2012 Apr;30(1):23-30. 10.5534/kja.2012.30.1.23.

Transforming Growth Factor-beta Type I Receptor Inhibitor Induces Functional and Morphologic Recovery in a Rat Model of Erectile Dysfunction and Cavernous Fibrosis

Affiliations
  • 1Department of Urology and National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea. jksuh@inha.ac.kr

Abstract

PURPOSE
To examine the effectiveness of small-molecule inhibitor of transforming growth factor-beta (TGF-beta) type I receptor, an activin receptor-like kinase 5 (ALK5), on erectile dysfunction (ED) in a rat model of cavernous fibrosis, in which fibrosis was induced by intracavernous injection of adenovirus expressing TGF-beta1 (Ad-TGF-beta1).
MATERIALS AND METHODS
Four-month-old Sprague-Dawley rats were divided into four groups (n=10 per group): age-matched controls without treatment, age-matched controls receiving intracavernous injection of LacZ adenovirus, and cavernous fibrosis rats receiving an intracavernous injection of saline or ALK5 inhibitor (5 mg/kg). ALK5 inhibitor or saline was administered on day 5 after injection of Ad-TGF-beta1. On day 30, erectile function was assessed by electrical stimulation of the cavernous nerve and the penis was then harvested for histologic studies (n=6 per group) and for the measurement of the hydroxyproline level (n=4 per group).
RESULTS
Ad-TGF-beta1-induced cavernous fibrosis rats treated with saline showed a significant decrease in cavernous smooth muscle and endothelial content, and an increase in collagen deposition, which resulted in profound deterioration of all erectile function parameters, such as the ratios of maximal intracavernous pressure (ICP), total ICP, and slope to mean arterial pressure. ALK5 inhibitor significantly restored erectile function in a rat model of cavernous fibrosis by increasing cavernous smooth muscle and endothelial content, and by blocking cavernous fibrosis.
CONCLUSIONS
The results suggest that inhibition of the TGF-beta pathway is a promising therapeutic strategy for the treatment of ED related to cavernous fibrosis from various causes.

Keyword

Erectile dysfunction; Fibrosis; Transforming growth factor beta; TGF-beta type I receptor
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