Effects and receptors of glucocorticoids in rat thymus cells and human peripheral lymphocytes.
Glucocorticoids are widely used for therapeutic purposes and have many toxic side effects. It seems likely that their physiological, therapeutic, and toxic effects are exerted through similar receptors and may be inherently inseparable. Lymphoid cells are targets for all these effects. With rat thymus cells in vitro, glucocorticoids immediately bind to cytoplasmic receptors, which are translocated to the nucleus, where they apparently induce messenger RNA for specific proteins that rapidly inhibit glucose transport. Protein and RNA metabolism are inhibited more slowly and eventually the cells die. The rate of formation of nuclear complexes and the timing of the hypothetical RNA-synthetic step are such as to suggest that the hormone-receptor complexes stimulate RNA synthesis in proportion to the rate at which they bind to nuclear sites rather than in proportion to the number of nuclear sites occupied. With normal peripheral human lymphocytes the rates of formation of hormone-receptor complexes are similar to those in rat thymocytes. The rate of onset of inhibition of glucose transport is lower, however, as is the rate of cytolysis. In human peripheral lymphocytes stimulated to undergo blast transformation with concanavalin A there is a dramatic increase in the number of glucocorticoid receptor sites per cell. This increase may be associated with a stage of the normal cell cycle, the mitogen stimulus inducing partial synchronization of the cell population. It has not been found, contrary to widespread belief, that mitogen stimulation renders cells insensitive to glucocorticoids.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003864:Depression, Chemical; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D005938:Glucocorticoids; D008934:Mitogens; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D005947:Glucose