Metallothionein synthesis and localization in relation to metal storage in rat liver during gestation

The metallothionein (MT) content of fetal rat liver was measured daily during the final week of gestation, by both cadmium saturation and polarographic methods. MT levels rise sharply at day 18 of gestation and continue to increase into the neonatal period. In late gestation, MT serves to bind Cu and Zn from the preexisting hepatic pools of these metals, as well as to accumulate additional amounts of both metals. The fetal MT is similar to the adult rat protein both in terms of its protein composition and metal-binding properties. Perinatally the Zn/MT ratio remains constant for several days suggesting a carefully regulated process. At birth, most of the hepatic Zn and a significant amount of hepatic Cu are bound to MT. Immunohistochemical localization MT shows a progressive increase in cytoplasmic MT with the appearance of nuclear MT by day 20 of gestation in fetal rat liver. The results are discussed in terms of a model for regulation of MT synthesis and for the metal storage role of MT in perinatal development.