SYNTHESIS OF AN HYPOTHESIS ADVOCATING A PROMINENT ROLE FOR THE THYROID-HORMONES IN MAMMALIAN LIVER-CELL PROLIFERATION INVIVO

Abstract

The accumulating evidence supporting a conspicuous role for the thyroid hormones and/or hepatic levels of nuclear T3 [triiodothyronine]-binding sites in hypatocyte proliferation in vivo is summarized. The hepatic nuclear binding sites for the iodothyronines were first described in 1972. Comparing a number of observations made on the hepatic levels of these nuclear T3-binding sites with models of liver cell proliferation, a striking relationship is now beginning to emerge. It seems that in many hepatomitogenic systems the levels of these nuclear binding sites become markedly reduced preceding the onset of enhanced DNA replication and mitosis. The hepatomitogenic systems described which do not involve a lowering in the levels of these nuclear binding sites appear to be predicated on raising the circulating levels of the thyroid hormones per se. How these 2 seemingly anomalous events can both produce the same proliferative effect on liver cells is not entirely clear. Equally vague as yet are the discrete genetic consequences of these proliferative initiators which lead to hepatocyte hyperplasia. There is some evidence that this proliferative controlling effect of the thyroid hormones on hepatocytes may also extend, in part, to hepatoma cells.