Hormonal Regulation of Liver Metallothionein Zinc: Independent and Synergistic Action of Glucagon and Glucocorticoids

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Abstract
Glucocorticoids may alter hepatic Zn metabolism. The induction of metallothionein synthesis seems to be one of the key regulatory steps involved. The influence of glucagon on liver metallothionein-bound Zn was examined. Glucagon (1.0 mg/kg) and/or dexamethasone (2.0 mg/kg) was administered to 175-225 g male rats. An independent, synergistic effect of glucagon which increased the binding of Zn to liver metallothionein induced by glucocorticoids was identified. The glucagon response was short-lived with a maximum 7 h after administration and a return to initial levels 7 h thereafter. A maximal increase in metallothionein-bound Zn in response to dexamethasone, a synthetic glucocorticoid, increased steadily to 21 h after administration. Administration of both the glucocorticoid and glucagon resulted in a significant, but short-lived, augmentation of the action of either hormone alone. Actinomycin D blocked the dexamethasone effect but had no effect on glucagon action, suggesting the latter does not involve de novo RNA synthesis. Changes in hepatic metallothionein-bound Zn may involve synergistic effects of glucagon and glucocorticoids which act through 2 separate, yet related mechanisms. The widespread role of glucagon and glucocorticoids in liver function and the regulation of hepatic Zn metabolism by multihormonal components were demonstrated.

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