Metallothionein mRNA induction in HeLa cells in response to zinc or dexamethasone is a primary induction response

Abstract

Metallothioneins (MTs) are low molecular weight, heavy metal binding proteins unique in their high cysteine content and high affinity for Zn²⁺, Cd²⁺, Hg²⁺, Ag²⁺ and Cu²⁺ (refs 1–3). The synthesis of MTs is induced by zinc or cadmium in the liver and kidney^4–8 and in cultured cells^9–12. More recently MT induction by the steroid hormone dexamethasone (Dex) has been demonstrated in HeLa cells¹³ and adrenalectomized rats¹⁴. Because glucocorticoid hormones lead to an intracellular accumulation of zinc^15–17, the question arises of whether the induction of MT gene expression by steroids is a ‘primary induction response’ (ref. 18), or due to elevated intracellular Zn²⁺. The glucocorticoid-induced transport of Zn²⁺ is dependent on concurrent protein synthesis^10,19. We now show that, in contrast to glucocorticoid-stimulated Zn²⁺ transport, the Zn²⁺ and Dex induction of translatable MT-mRNA is independent of concomitant protein synthesis but not RNA synthesis; that is, MT induction by either agent is a primary induction response¹⁸.