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Effect of Progesterone on Cell Division in Chemically Induced Endometrial Hyperplasia and Adenocarcinoma in Mice¹

Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamikyo-ku, Kyoto 602, Japan

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 hyperplasia 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 administered to the mice caused a significant reduction in labeling with [³H]thymidine in nonatypical hyperplasia and moderate atypical hyperplasia, compared to that for the untreated mice. In marked atypical hyperplasia and adenocarcinoma, irrespective of the histological grade, labeling was not reduced.

With the high dose of progesterone, marked morphological alterations with degenerative changes were observed in atypical hyperplasia and in differentiated adenocarcinoma. However, cancer cells were still maximally labeled. The results indicate that the effect of progesterone on nonatypical hyperplasia and moderate atypical hyperplasia is mitotic arrest, whereas the effect on marked atypical hyperplasia and adenocarcinoma is morphological and cytological alterations.

¹ Supported in part by a Grant-in-Aid from the Japan Ministry of Education, Science, and Culture, awarded to Dr. H. Okada.

² Present address: Department of Gynecology-Obstetrics. State University of New York at Buffalo, School of Medicine, Buffalo General Hospital, 100 High Street, Buffalo, N. Y. 14203.

Received 5/16/77. Accepted 10/ 5/77.