Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes

The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were in a more stringent environment. Slight changes in ratios of adenine and guanine nucleotides appear to account for the reordering of metabolic priorities that occurs, with processes related to growth and development curtailed in favor of those more essential to immediate cell survival. The lethal glucocorticoid actions appear to be the result of the operation of separate mechanisms (unrelated to energy metabolism) that lead to lethal attack at the level of the nuclear membrane. Resistance to the lethal effects appears to occur via the selection (in the case of cancer cells where the animal or patient is undergoing chemotherapy with glucocorticoids) or the normal development (in the case of immunologically noncommitted thymocytes progressing to immunologically committed ones) of cells with hardier membranes. This progression is associated with a change in a few cellular proteins. One such protein appears identical in both kinds of cells, offering itself as a candidate for an intracellular mechanism conferring resistance. Evidence is also presented for the appearance of hormone-induced proteins that could be metabolic regulators that mediate the individual cellular and biochemical actions of glucocorticoids. It is proposed that toxins could alter cellular metabolism through mechanisms similar to those utilized by steroid hormones, or possibly alter the sensitivity of cells to steroids, or vice versa.