Glucocorticoid hormone receptor mediated induction of metallothionein synthesis in HeLa cells

Abstract

HeLa cells grown in chemically defined medium lacking glucocorticoids synthesize metallothioneins, low molecular‐weight heavy‐metal binding proteins. Dexamethasone and hydrocortisone increase the rate of metal‐lothionein synthesis five‐ to ten‐fold. Maximal induction is achieved with 10^–8M dexamethasone and 10^–7M hydrocortisone. Half‐maximal induction is achieved at 5 ± 10^–9M dexamethasone and 5 ± 10^–8M hydrocortisone. Although carried for many generations in the absence of any glucocorticoids, HeLa cells (clone S) contain 25,000 specific ³H‐dexamethasone receptors that translocate into the nucleus after one hour of incubation. ³H‐dexamethasone binds to a single class of receptors with an apparent Kd = 18.8 nM. A variety of steroids can be classified into three classes, based on their effect on metallothionein synthesis: (a) full agonists (optimal inducers), (b) intermediate effectors which have either partial agonist or antagonist activities, and (c) inactive steroids. There is a correlation between the effects on metallothionein synthesis of different steroids and their ability to compete with ³H‐dexamethasone binding. We conclude that metallothionein is induced in HeLa cells by a glucocorticoid receptor mediated mechanism.