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Abstract 43

Matrix Metalloprotease Activities in the Pathogenesis of Estradiol-lnduced Nonbacterial Prostatitis in the Lateral Lobe of the Wistar Rat

MJ Wilson,1,2 M Woodson, M Sinha3

VA Medical Center and Departments of Laboratory Medicine and Pathology, 2Urologic Surgery and 3Genetics and Cell and Developmental Biology, University of Minnesota

Chronic nonbacterial prostatitis develops with age in the lateral lobe of the prostate in some strains of rat. This lobe-specific prostatitis can be induced by chronic estrogen treatment. We used the model of Robinette (Prostate 12:271-286,1988) of estrogen treatment of castrated male Wistar rats to examine the role of proteases in the pathogenesis of the induced chronic nonbacterial prostatitis. Male Wistar rats 90 days of age (8 rats/group) were castrated and implanted 8 days later with 1 cm sialistic tubings containing estradiol 17p (E2). Some animals received 5 cm silastic tubings of dihydrotestosterone (DHT) or testosterone (T) on day 22 and all untreated control and experimental animals were sacrificed on day 36 of the protocol. Matrix metalloprotease (MMP) activities were determined by SDS-gelatinacrylamide gel zymography.

A high molecular weight protease activity (>160 kDa) was detected in the lateral prostate lobe of untreated control animals. However, there were prominent MMP activities in the lateral lobes of E2-treated rats. These included both the active

(55 and 81 kDa) and proenzyme (72 and 92 kDa) forms of MMP-2 and MMP-9, respectively. These activities were strongly attenuated by treatment of T with E2-, but only weekly so by DHT with E2. In comparison to the lateral lobe, there were minimal effects of E2 on MMP activities in the ventral and dorsal prostatic lobes. In the ventral prostate, the 72 kDa proMMP-2 was detected in untreated rats. This activity was reduced in E2-treated castrates but increased in those given T or DHT with E2. Low activities of the pro and active form of MMP-2 and the active form of MMP-9 were detected in the dorsal prostate of untreated rats. These activities were not changed in E2- treated castrates. Thus MMPs, which probably originate from leukocytes mobilized in the inflammatory response, help mediate accompanying epithelial atrophy and proliferation of the fibromuscular stroma in the lateral prostate.

(Supported in part by research funds of the Department of Veterans Affairs.)