Effect of dexamethasone pretreatment on the dexamethasone-dependent induction of tyrosine aminotransferase activity in primary cultured rat hepatocytes.

The effect of dexamethasone (Dex) pretreatment on the Dex-dependent induction of tyrosine aminotransferase (TAT) activity was studied in primary cultured rat hepatocytes. The extent of the Dex-dependent induction of TAT activity decreased during culture in untreated cells. Dex pretreatment prevented this decrease. A Scatchard plot analysis of the results of a [3H]Dex binding assay showed that hepatocytes cultured for 2.5 h possessed both high and low affinity binding sites in their cytosols. The number of both high and low affinity binding sites decreased during culture for a further 24 h in untreated cells. Dex pretreatment partly prevented the decrease in low affinity binding sites but had no effect on the decrease in high affinity binding sites. These results show that Dex pretreatment counteracts the usual decrease in the inducibility of TAT activity, and suggest that this action of Dex may be due to the maintenance of low affinity binding sites. These results also suggest that low affinity binding sites could possibly mediate the biological response to Dex.