| Abstrakt: |
Recent evidence suggests glucocorticoids alter hepatic zinc metabolism. The induction of metallothionein synthesis seems to be one of the key regulatory steps involved. The experiments reported here were designed to examine the influence of glucagon on liver metallothionein-bound zinc. 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 zinc to liver metallothionein induced by glucocorticoids was identified. The glucagon response was short lived with a maximum 7 hr after administration and a return to initial levels 7 hr thereafter. A maximal increase in metallothionein-bound zinc in response to dexamethasone, a synthetic glucocorticoid, increased steadily to 21 hr 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 novoRNA synthesis. These results suggest that changes in hepatic metallothionein-bound zinc involve synergistic effects of glucagon and glucocorticoids which act through two separate, yet related mechanisms. These findings expand our view of the widespread role of glucagon and glucocorticoids in liver function and demonstrate that the regulation of hepatic zinc metabolism has multihormonal components. |
