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.
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D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D051379:Mice; D010911:Pituitary Neoplasms; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects
D000621:Aminoisobutyric Acids; D005938:Glucocorticoids; D011506:Proteins; D011965:Receptors, Glucocorticoid; C100049:2-aminoisobutyric acid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D007930:Leucine