Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland.

Abstract

Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms of action of BTX-A on the prostate. Adult male Sprague-Dawley rats were injected with varying doses of BTX-A into the prostate and the prostates were harvested after 1 or 2 weeks. The effects of BTX-A on prostate histology, and the proliferative and apoptotic indexes were determined using hematoxylin and eosin staining, proliferative cell nuclear antigen staining and TUNEL staining, respectively. Changes in alpha(1A) adrenergic receptor and androgen receptor were evaluated by Western blotting. One week after BTX-A injection generalized prostate atrophy was observed. There was a significant increase in apoptotic cells (12, 16 and 22-fold), and decrease in proliferative cells (38%, 77% and 80%) and alpha(1A) adrenergic receptor (13%, 80% and 81%) for 5, 10 and 20 U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment. BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating alpha(1A) adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia.