Effects of Estrogen Replacement Therapy on the Expression of Apoptosis-Related Genes in Old Female Rats

Effects of estradiol (E2) on the urinary bladder of old female rats were investigated by morphological, immunohistochemical and apoptosis-related gene analysis. Sixteen-month-old female Wistar rats were divided into the following 5 groups: normal controls; rats replaced with low-dose E2 for 2 and 4 weeks, respectively; and rats replaced with high-dose E2 for 2 and 4 weeks, respectively. After treatment, the bladders were removed, weighed and stained with hematoxylin and eosin, and immunostained by monoclonal antibodies against Bcl-2 and Bax proteins. Further, the expression of apoptosis-related genes bcl-2 and bax were investigated by PCR analysis, and evaluated by computerized quantification. Immunostained bladders showed no difference between control and E2-replaced rats in reactivity against Bcl-2 protein. In contrast, against Bax protein, control rats showed immunoreactivity, whereas E2-replaced rats showed little reactivity. Upon mRNA analysis, the expression of bax mRNA was suppressed in the E2-replaced rats as compared with the controls, though the expression of bcl-2 mRNA showed no difference among groups. These results suggest that E2 administration affects the expression of apoptosis-related genes and suppressees apoptotic action, and that these changes could consequently alter voiding behavior.