Modulation of glucocorticoid receptors by mitogenic stimuli, glucocorticoids and retinoids in normal human cultured T cells.
Human T lymphocytes can be maintained in cell culture by the addition of conditioned medium (CM) containing a T cell growth factor (TCGF). This system provides an opportunity to study the presence and modulation of glucocorticoid receptors (GR) by various factors in these cells. GR were present in T cells grown from each of 22 normal individuals; the binding capacity (mean = 3851 +/- 2880 sites/cell) and affinity (Kd = 7.4 X 10(-9)) were similar in rested cultured T cells (CTC) to those reported in peripheral blood T lymphocytes. Treatment of rested CTC with stimuli such as phytohemagglutinin (PHA), CM, or 12-O-tetradecanoylphorbol-13-acetate (TPA) results in a mean increase in GR binding capacity of 3.1-, 3.2- or 2.4-fold respectively without modification of binding affinity. Using an exchange assay to measure occupied and unoccupied GR, we examined the effects of cortisol on its own receptor. Treatment of rested CTC with 10(-7) M cortisol for 24 h decreased GR by more than 50%. Cortisol treatment also blocked the induction of GR by PHA and CM. Since retinoids have been shown to modulate the immune response and to alter the effects of PHA and phorbol esters on lymphocytes, we examined their effects on GR. Retinol decreased GR activity in CTC but only at concentrations which inhibit cell growth. It is concluded that GR activity in human T cells can be modulated by several important factors involved in lymphocyte function.
D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
D008934:Mitogens; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014801:Vitamin A; D014212:Tretinoin; D003907:Dexamethasone; D006854:Hydrocortisone