Transforming growth factor-beta(1) (TGF-beta(1)) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo

Purpose: The pleotropic cytokine TGF-beta(1) which induces connective tissu e synthesis, and inhibits the growth of smooth muscle cells, has been impli cated in corpus cavernosum fibrosis. The objective of this study was to det ermine the dose and time dependence of TGF-beta(1) as an active agent in pe nile corporal fibrosis in an animal model. Materials and Methods: A time release method of delivery was developed usin g sodium alginate microspheres containing recombinant human (rh) TGF-beta(1 ). New Zealand White rabbits were injected intracorporally with a single al ginate microsphere either with or without rh-TGF-beta(1). Dosage was varied from 325 to 1500 ng./bead. Animals were sacrificed at either three or five days post injection and the penises removed en bloc, examined, and process ed for quantitative histomorphometric analysis, staining the sections with Masson's trichrome. Results: Alginate microspheres containing [I-125]-rh-TGF-beta(1) showed slo w-release kinetics (t(1/2) = 10.5 hours). Histomorphometric analysis of 60 sets of high powered fields/treatment/animal showed dose dependent decrease s in percentage of corporal smooth muscle with TGF-beta(1) treatment (750 t o 1500 ng./bead). Placebo (alginate microspheres alone) had trabecular smoo th muscle content comparable to values previously reported for untreated ra bbit corpus cavernosum. Conclusions: This study confirms that TGF-beta(1) induces fibrosis in situ by altering connective tissue synthesis and hence the structure of the corp us cavernosum. Injection of rh-TGF-beta(1) impregnated alginate microsphere s into the corpus cavernosum resulted in dose-dependent decreases in percen tage of corporal smooth muscle.