Hyperproliferative hepatocellular alterations after intraportal transplantation of thyroid follicles

The thyroid hormone 3,5,3'-triiodo-L-thyronine (T3) is a strong direct hepa tocyte mitogen in vivo. The effects of T3 resemble those of peroxisome prol iferators, which are known to induce hepatocellular tumors in rats. With th e aim of studying long-term local effects of thyroid hormones on liver pare nchyma, small pieces of thyroid tissue were transplanted via the portal vei ns into the livers of thyroidectomized male Lewis rats. At 1 week, 5 weeks, 5 months, and 18 months after transplantation, the transplants were found to proliferate, to synthesize thyroglobulin, and to release thyroxine and T 3. At 5 and 18 months after transplantation, the hepatocytes of the liver a cini downstream of the transplanted follicles showed an increase in cytopla smic basophilia, a loss of glycogen, an enlargement and hyperchromasia of t heir nuclei, and a strong increase in cell turnover compared with unaltered liver acini. The altered hepatocytes exhibited an increase in the activiti es of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, malic enzym e, mitochondrial glycerol-5-phosphate dehydrogenase, cytochrome-c-oxidase, and acid phosphatase; the activities of glycogen synthase and glycogen phos phorylase were strongly decreased. The hepatocytic alterations downstream o f the transplanted follicles could be explained by effects of T3. On the ot her hand, they resembled alterations characteristic of amphophilic preneopl astic liver foci observed in different models of hepatocarcinogenesis.