INVASIVE PITUITARY-TUMORS IN FEMALE F344 RATS INDUCED BY ESTRADIOL DIPROPIONATE

To clarify the histopathological progression of invasive tumors in the pituitary pars distalis due to estrogen, female Fischer 344 (F344) ra ts were treated subcutaneously with 5 mg/animal of estradiol dipropion ate (ED) once every 2 wk for 13 wk. The animals were killed serially a t 2-wk intervals during the investigation. The pituitaries with surrou nding tissues were examined light microscopically. At week 7, pituitar y cells showed proliferation and atypia with formation of blood-filled spaces. Lesions with these characteristics were diagnosed as adenomas . At week 9 or later neoplastic cells exhibited extensive proliferatio n and infiltration into the surrounding tissues, suggesting developmen t of carcinoma. Both proliferating cell nuclear antigen (PCNA) and 5-b romo-2'-deoxyuridine (BrdU) labeling index, markers of cell proliferat ion, were significantly increased in animals with adenoma or carcinoma . To detect sequential changes in pituitary weight, its signal intensi ty was periodically monitored in identical rats by using magnetic reso nance (MR) imaging. The estimated pituitary weights revealed by MR ima ging were comparable to the tumor wrights obtained from rats at schedu led sacrifices. These results indicate that ED possesses the potential to cause carcinoma in rat pituitary and MR imaging is an effective to ol for estimating the pituitary weight.