Effect of transforming growth factor-β₁ on proliferation and death of rat prostatic cells

The ability of transforming growth factor B₁ (TGFβ₁) to inhibit proliferation and activate death of rat ventral prostatic glandular cells was tested both in vivo and in vitro. In vivo administration of 50 ng TGFβ₁/day directly to the regressed ventral prostate of previously castrated male rats had no effect on the proliferative regrowth of the prostatic glandular cells induced by exogeneous androgen replacement. In addition, androgen-stimulated ventral prostatic cell proliferation in vitro in organ culture was not affected by exposure to 0.1-20 ng/ml TGFβ₁. In contrast in vivo administration of 50 ng TGFβ₁/day directly to the ventral prostate of intact noncastrated male rats resulted in the death of about 25% of the prostatic glandular cells within 7 days of treatment. Such TGFβ₁ treatment did not lower serum testosterone, nor did it affect the size or DNA content of the seminal vesicles, demonstrating the local nature of the response. Likewise, in androgen-maintained ventral prostate organ cultures in vitro, there was a dose-response relationship between glandular cell death and TGFβ₁ concentration in the medium. These results demonstrate that TGFβ₁ can induce the death of androgen-dependent prostatic glandular cells even when physiological levels of androgen are present. Previous studies have demonstrated that both the receptor and the mRNA for TGFβ₁ increase rapidly in the ventral prostate after castration. Taken with the present data, these results suggest that TGFβ₁ may be a physiological intermediate in the programmed cell death of rat prostatic glandular cells activated after androgen ablation.