Induction of Metallothionein in HeLa Cells by Dexamethasone and Zinc

Metallothioneins are induced by both Zn2+ and dexamethasone in HeLa cells grown in serum-free medium. Dexamethasone is able to induce metallothionein synthesis in HeLa cells in virtually zinc-free medium ([Zn2+] = .01 microM). The presence of dexamethasone does not shift the dose/response curve for metallothionein induction by Zn2+, further indicating that the two inducers work through independent mechanisms. Dexamethasone stimulates Zn2+ uptake 1.7-fold over 24 h. However, there is no increase in Zn2+ uptake during the first 4 h. In contrast, metallothionein synthesis in response to either Zn2+ or dexamethasone is clearly observable within 4 h of exposure to either inducer. The increased intracellular 65Zn2+ content observed at 24 h is completely accounted for by the increased level of metal bound to metallothionein. In a continuous labeling experiment the rate of synthesis of metallothionein reached a steady state after about 4 h, in response to either inducer. The lag period was identical for both dexamethasone and Zn2+, with similarly shaped induction curves. Induction by dexamethasone, but not by Zn2+, was inhibited by progesterone. Zn2+ and dexamethasone appear to induce metallothionein synthesis in HeLa cells by mechanisms independent of one another.