Differential sensitivity of isolated rat thymocytes to glucocorticoids following concanavalin A stimulation

Abstract

Concanavalin A (Con A) rapidly stimulates leucine incorporation into trichloroacetic acid (TCA) precipitable, but not TCA soluble material in isolated rat thymocytes. This stimulation of leucine incorporation by Con A is dose dependent, time dependent, and is inhibited by the addition of cycloheximide. In non mitogen stimulated thymocytes, cortisol (10 −6 M) inhibits leucine incorporation into protein by 30%, whereas in Con A stimulated cells, cortisol inhibits leucine incorporation by 50%. The cortisol effect in Con A stimulated cells is present when cortisol and Con A are added simultaneously, is diminished when cortisol is added at intervals after Con A and is dependent on the concentration of cortisol administered. The inhibitory effect of cortisol on leucine incorporation is dose and time dependent in both control and Con A treated cells. The magnitude of the cortisol effect does not differ in control and Con A stimulated thymocytes for the first 3 h of steroid exposure, after which time a significant increase in the glucocorticoid effect occurs only in the Con A stimulated cells. This increased response to cortisol occurs at a time which is coincident with the mean maximal response of these cells to Con A alone. Both progesterone and cortexolone (10 −6 M) inhibit leucine incorporation in control cells only slightly. The magnitude of these effects does not change by stimulation of the thymocytes with Con A. Under the conditions of these experiments, the rate of accumulation and the levels of nuclear glucocorticoid receptors are the same in both control and Con A stimulated thymocytes. These data indicate that thymocyte responsiveness to glucocorticoid is increased following exposure to concanavalin A. This enhanced response to glucocorticoid probably occurs subsequent to nuclear accumulation of steroid receptor complexes.