Hormonal Deinduction of Tyrosine Aminotransferase

Summary

The effects of several antagonists of glucocorticoid action on a line of hepatoma cells (HTC strain) have been studied in order to determine their mechanism of action. The induction of tyrosine aminotransferase by dexamethasone can be partially or totally inhibited if an antagonist is added simultaneously with dexamethasone or some time later. Antagonists, even if they have as much affinity for the cytoplasmic receptor as dexamethasone, must be administered at a 100-fold excess as compared to dexamethasone. Their receptor binding kinetics are not identical to those of inducer steroids; moreover there is no correlation between relative binding affinities and anti-inducing capacities. A short contact between the cells and the antagonist is sufficient to obtain a full antagonistic effect, but the antagonist is inactive if administered and removed from the cells before induction. An interpretation is suggested, considering these results which do not find a satisfactory explanation in the classical theory of receptor action.

Key-Words:

Tyrosine Aminotransferase - Glucocorticoid Hormones - Antagonists - Receptor Binding - Hepatoma Cells