Effect of progesterone on cell division in chemically induced endometrial hyperplasia and adenocarcinoma in mice.

Cotton string coated with 3-methylcholanthrene (MCA) was implanted in the uterine cavity of ICR mice to induce endometrial hyperplasia and adenocarcinoma. A low dose (total, 2.5 mg) or a high dose (total, 35 mg) of progesterone was administered to the mice at various times during a period of 4 to 40 weeks after MCA application. After serial labeling with [3H]thymidine, the mice were sacrificed, and thymidine-labeling index values of endometrial hyperpla sia and adenocarcinoma both in the progesterone-treated and the untreated mice were investigated by autoradiographic techniques. In mice that had been implanted with MCA, there was a progressive increase of hyperplasia and neoplasia as a function of time. The low dose of progesterone adminis tered to the mice caused a significant reduction in labeling with [3H]thymidine in nonatypical hyperplasia and moder ate atypical hyperplasia, compared to that for the un treated mice. In marked atypical hyperplasia and adeno carcinoma, irrespective of the histolÃ3gica! grade, labeling was not reduced. With the high dose of progesterone, marked morpholog ical alterations with degenerative changes were observed in atypical hyperplasia and in differentiated adenocarci noma. However, cancer cells were still maximally labeled. The results indicate that the effect of progesterone on nonatypical hyperplasia and moderate atypical hyperpla sia is mitotic arrest, whereas the effect on marked atypical hyperplasia and adenocarcinoma is morphological and cytological alterations.