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Regulation of Intestinal Metallothionein Biosynthesis in Rats by Dietary Zinc^1,2,

Department of Nutrition, Rutgers University, New Brunswick, NJ 08903

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 <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 content 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.

KEY WORDS: • intestine • dietary zinc • metallothionein induction • mRNA

¹ Supported by Grant No. AM18555 from the National Institute of Arthritis, Metabolism and Digestive Diseases, the Charles and Johanna Busch Memorial Fund of Rutgers University and as Project No. 14112 of the New Jersey Agricultural Experiment Station.

² Presented in part at the American Institute of Nutrition Meeting, Anaheim, CA, April 1980. Fed. Proc. 39, abs. #885.

³ Present address: Department of Poultry Science, Cornell University, Ithaca, NY.

⁴ To whom reprint requests should be sent.

Manuscript received 18 February 1981.

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