Interactions of glucocorticoids with the AtT-20 cell: effect on protein accumulation.

In order to investigate the mechanism through which glucocorticoids downregulate the number of their own receptors in the AtT-20 cell, the effect of glucocorticoids on cell protein metabolism was studied. Glucocorticoids were found to inhibit cellular protein accumulation when included in long-term cultures. The concentrations of agonists that cause a mid-maximal effect are similar to those needed to half-saturate the glucocorticoid receptor, suggesting that the growth-inhibiting effect is receptor-mediated. Two-dimensional electrophoresis of cytosolic extracts of treated and control cells suggested that the effect reflected a general suppression of overall protein accumulation rather than a selective effect on certain classes. Comparison of the protein to DNA ratio of control and dexamethasone-treated cells showed that the latter have higher ratios suggesting that cell composition may be altered by agonists. However, time-course studies of this effect indicated that this is basically an expression of a glucocorticoid effect on cell growth rather than a selective effect on protein metabolism. It is concluded that glucocorticoids inhibit overall AtT-20 cell growth and that this, in turn, manifests itself as a decrease in the rate of protein accumulation. It is suggested that this change in protein metabolism may be a minor component in the mechanism through which glucocorticoids decrease AtT-20 cell ACTH secretion and glucocorticoid receptor number.