ONTOGENIC CHANGES IN HEPATIC METALLOTHIONEIN ISOFORMS IN PRENATAL AND NEWBORN RATS

The relative quantities of the two metallothionein isoforms (MT-1 and MT-2) in prenatal and newborn rat livers have been quantified using a competitive enzyme-linked immunosorbent assay with two specific polyclonal antisera. Both MT isoforms were detected in fetal liver on gestation day 16 and their levels continued to increase into the neonatal period. A concomitant increase was observed in plasma MT levels in the pregnant rats. The level of MT-2 was higher (75%) than that of MT-1 in the liver of both prenatal and neonatal rats. Both hepatic MT isoforms showed a significant correlation (P < 0.05) with the hepatic Zn level. Immunohistochemical localization of MT isoforms showed no apparent difference in intracellular distribution. Both MT isoforms were mainly cytoplasmic in fetal rat liver. Intense intranuclear staining was observed in newborn rat liver when the total MT concentration reached a maximum of over 1 mg MT/g tissue. The nuclear MT staining decreased with age, and at day 7, approximately equal concentrations of MT were found in nucleus and cytoplasm. When the newborn rats (1 day old) were injected with Zn (10 mg/kg), both MT isoforms were induced on days 2 and 7. Injection of Cd (I mg/kg) increased the hepatic MT levels only on day 7. The level of MT-2 remained higher than that of MT-1 in all cases. These results suggest that both MT isoforms play a similar role in the metabolism of Zn during early development and the relative abundance of the MT isoforms may be a species-specific phenomenon.