Reciprocal relationship between the levels of the hepatic nuclear binding sites for T3 and DNA replication in the liver of the rat: a possible unifying concept.

Administration of low levels of thyroid hormone (T3), subsequent to adrenalectomy, cause a pronounced proliferative response in rat liver, as judged by enhanced DNA replication. Adrenalectomy of the rat causes a reduction in the maximal nuclear binding capacity for T3 in the liver, similar to that produced by 70% hepatectomy of the rat, the former decrease lagging approximately 12 h after the latter. Similar kinetics are reported for the enhancement of hepatic nuclear DNA synthesis in these two groups of animals. Both of these effects in either group of surgically-treated animals are obviated by the injection of dexamethasone. Other reports are cited indicating that a reciprocal cause-and-effect relationship may exist between the lowering of the hepatic nuclear maximal binding capacity for T3 and subsequent enhanced hepatic DNA replication in a number of other rat model systems. It is suggested that enhanced hepatic cell proliferation in the rat may be effected by either raising the circulating levels of the thyroid hormones or by lowering the levels of the hepatic nuclear binding sites for these agents.