Expression of proliferating cell nuclear antigen in luminal epithelium during the growth and regression of rat uterus

Proliferating cell nuclear antigen (PCNA), a processivity factor of DNA syn thesis, has often been used as a marker that reveals proliferating cells. H owever, it also plays a role other than in DNA replication. The aim of this study was to examine the relationship between the expression of PCNA and c ell proliferation, and also its relation to cell death in the uterine epith elium under various hormonal conditions. Rats with regular estrous cycles w ere killed at various stages of the cycle, and their uteri were removed for the detection of PCNA and apoptosis by immunohistochemical and terminal de oxynucleotidyl transferase-mediated nick end-label staining respectively. T here was an inverse relationship between the expression of PCNA and apoptos is in the uterine epithelium during the estrous cycle. From diestrus to pro estrus, the expression of PCNA increased, and few apoptotic cells were dete cted in the luminal epithelium. However, at estrus, apoptosis occurred mark edly, and the expression of PCNA disappeared. To study further the effects of estrogen on PCNA expression and cell growth in the uterus, rats were ova riectomized and then implanted s.c. with estrogen capsules 2 weeks later. I n ovariectomized rats, only a few PCNA-positive cells were observed in the uterine epithelium. After estrogen treatment, PCNA was expressed strongly i n the luminal and glandular epithelia. In these rats, the removal of estrog en capsules resulted in apoptotic death and surprisingly strong PCNA expres sion in the cells of luminal epithelium. Our results demonstrate that PCNA is expressed not only in the estrogen-stimulated uterine growth, but also i n the processes of regression induced by the withdrawal of estrogen. Althou gh the expression of PCNA has been reported to represent cell proliferation , our results implicate functions other than cell replication for PCNA in t he uterus.