Induction of hepatic metallothionein by feeding zinc to rats of depleted zinc status

Induction of hepatic metallothionein was investigated in zinc-depleted rats after a single feeding (via stomach tube) of a complete diet with or without supplemental zinc. Subsequent to a maximum elevation in serum zinc (3.25 micrograms/ml) at 3 h, the rate of metallothionein synthesis increased 4.5-fold by 10 h after feeding. Changes in the rate of metallothionein synthesis coincided with similar changes in the level of translatable mRNA coding for metallothionein. Accumulation in liver of Zn2+ as metallothionein rose to a maximum by 12 h after diet administration and thereafter remained constant. Radioactive zinc (65Zn) included in the diet rapidly associated with newly formed metallothionein. Unlike Zn2+, 65Zn exhibited marked fluctuations within the 24-h period following feeding, indicating that zinc associated with metallothionein may be capable of exchange and/or dissociation. Changes in total liver 65Zn were accompanied by concomitant changes in metallothionein-bound 65Zn. This study has related (temporally) the metabolism of dietary zinc to the induction, apparently via transcription of mRNA, of hepatic metallothionein.