Changes in rat hepatocyte plasma membranes caused by synthetic estrogens

Livers of rats treated with ethynyl estradiol show hepatocyte swelling, nuclear enlargement, and an increase in size and numbers of nucleoli. Mitotic figures are frequent and there is occasional hepatocyte necrosis. Thin sections (1-micron. thick) show separation of cells with gaps between. Ultrastructurally, these gaps are occupied by cell membrane microville. These microvilli are not a normal feature on cell borders between adjacent hepatocytes. Similar anomalous microvilli are a feature of hepatocytes in regenerating nodules of cirrhosis, regenerating hepatocytes following partial hepatectomy, and in embryonic liver tissue. The significance of this finding and the known relationship of contraceptive agents and liver tumors is discussed.