Biosynthesis and metabolism of metallothionein in rat during perinatal development

Although high concentrations of zinc (Zn) and metallothionein (MT) have been detected in the livers of many newborn mammals, the factors affecting the biosynthesis and metabolism of MT are not yet clearly defined. In rat liver, MT levels rise sharply at the 18th day of gestation and continue to increase into the neonatal period. In late gestation, MT serves to bind Cu and Zn from the pre-existing pools of these metals, as well as to accumulate additional amounts of Zn. The high levels of Zn and MT are maintained for about two weeks in neonates and then decreased to adult levels at weaning. Perinatally, the Zn/MT ratio remains constant for several days, suggesting a carefully regulated process. Injection of ZnSO4 into newborn rats results in increased accumulation of Zn and induced synthesis of MT in liver, while injection of CdCl2 has no effect. When pregnant rats are fed with a Zn-D diet, there are marked reductions in the levels of both hepatic Zn and MT in neonates. Similar studies with copper and iron deficient diets have no effect on high hepatic MT and Zn levels in newborn rats. Immunohistochemical localization of MT using a specific antibody to MT shows a progressive increase in cytoplasmic MT with the appearance of nuclear MT by day 20 of gestation in fetal rat liver. The presence of MT in the nucleus of hepatocytes is maintained in neonates for several days and later MT is detected in the cytoplasm during postnatal development.