Regulation of intestinal metallothionein biosynthesis in rats by dietary zinc.

Response of intestinal metallothionein and zinc to dietary zinc intake was investigated in zinc-depleted rats, after a single feeding by stomach tube of a purified diet supplemented with either 125 ppm zinc or less than 1 ppm zinc. Serum zinc concentration was maximal 3 hours post-feeding, then stabilized at lower levels returning to baseline concentration by 18 hours. Mucosal zinc concentration rose to a maximum by 6 hours after feeding and plateaued at slightly lower levels thereafter, due to association of this zinc with metallothionein. The rate of metallothionein synthesis rose 4-fold, 6-9 hours after feeding, coinciding with the maximal contest of translatable metallothionein mRNA concentration. Together, these findings provide strong evidence for a regulatory role of metallothionein in zinc absorption and homeostasis, where dietary zinc influences subcellular events in mucosa affecting regulation of the metallothionein gene. These events include the induction of de novo metallothionein synthesis, preceded by an increase in translatable mRNA specific for this metalloprotein, and followed by a reduction in zinc absorption simultaneous with the binding of absorbed zinc with newly synthesized thionein polypeptides.