Changes in Apoptosis-Related Genes (Bcl-2, Bax) in the Urethras of Old Female Rats Following Estrogen Replace- ment

Following estrogen replacement in old female rats, changes in apoptosis-related genes (Bcl-2, Bax) in the urethra were investigated by immunohistochemical and RT-PCR analysis. A total of 40 old (16-month-old) female Wistar rats were divided into the following 5 groups: normal controls; rats replaced with low-dose estradiol (E2) for 2 and 4 weeks, respectively; and rats replaced with high-dose E2 for 2 and 4 weeks, respectively. After treatment, the urethras were removed, weighed and stained with hematoxylin and eosin, and then immunohistochemical stainings of Bcl-2 and Bax were performed. In addition, the expressions of the apoptosis-related genes bcl-2 and bax were investigated by PCR analysis, and then evaluated by computerized quantification. In the E2-replaced rats, the immunostained urethras showed little immunoreactivity against the Bcl-2 protein, and in the control rats, no reactivity was seen. In contrast, the control rats showed immunoreactivity against the Bax protein, whereas the E2-replaced rats showed little reactivity. Upon mRNA analysis, the expression of bcl-2 mRNA was uprisen in rats in the high-dose E2 for 4 weeks group as compared with the controls, but the expression of bax mRNA was suppressed in the E2-replaced rats as compared with the controls. As these results suggest, estrogen replacement up-regulated the expression of bcl-2 mRNA and down-regulated the expression of bax mRNA, which might suppress the apoptic action: these changes might alter lower urinary tract findings.