Down regulation of Bcl-2 is the first step on Fas-mediated apoptosis of male reproductive tract.

Suppression of apoptosis by Bcl-2, an oncogene product, has been previously reported. Although the down regulation of Bcl-2 has been encountered in various types of apoptosis, the time course of changes in the expression of Bcl-2 has yet to be determined. In the present study, we established and analysed an in vivo model of apoptosis. The mouse male reproductive tract, specifically the prostate and epididymis, which is regulated by sex steroid hormones, especially testosterone, showed regression induced by chromosomal DNA fragmentation, apoptotic cell death, after gonadectomy. Following this apoptosis, down regulation of Bcl-2 and the new expression of Fas were seen. Using functional Fas-lacking mice, we demonstrated that this regression of the male reproductive tract is triggered by Fas-mediated apoptosis. In addition, time course experiments revealed that down regulation of Bcl-2 when apoptosis occurs heralds Fas expression. We propose here that apoptotic death signal transduction in total involve, a number of steps, the first and most important of which is down regulation of Bcl-2.