Glucocorticoids and cyclic AMP exert dramatic effects on the proliferation and viability of murine T lymphocytes through unknown mechanisms. To identify gene products which might be involved in glucocorticoid-induced responses in lymphoid cells, we constructed a XcDNA library prepared from murine thymoma WEHI-7TG cells treated for 5 h with glucocorticoids and forskolin. The library was screened with a subtracted cDNA probe enriched for sequences induced by the two drugs, and cDNA clones representing 11 different inducible genes were isolated. The pattern of expression in BALB/c mouse tissues was examined for each cDNA clone. We have identified two clones that hybridized to mRNAs detected exclusively in the thymus. Other clones were identified that demonstrated tissue-specific gene expression in heart, brain, brain and thymus, or lymphoid tissue (spleen and thymus). The kinetics of induction by dexamethasone and forskolin were examined for each gene. The majority of the cDNA clones hybridized to mRNAs that were regulated by glucocorticoids and forskolin, two were regulated only by glucocorticoids, and three hybridized to mRNAs that required both drugs for induction. Inhibition of protein synthesis by cycloheximide resulted in the induction of all mRNAs that were inducible by glucocorticoids. Preliminary sequence analysis of four of the 11 cDNAs suggests that two cDNAs represent previously undescribed genes while two others correspond to the mouse VL30 retrovirus-like element and the mouse homolog of chondroitin sulfate proteoglycan core protein.Glucocorticoids induce cytolysis in susceptible lymphocyte populations, including immature thymocytes and certain leukemias and lymphomas. Steroid-induced cell death is thought to occur through the activation of an endogenous suicide process. Glucocorticoid treatment of murine lymphocytes results in severe alterations in cellular metabolism which include an inhibition of glucose transport (50), increased RNA (14) and protein (44) degradation, a rise in intracellular calcium levels (37), and decreased incorporation of thymidine into DNA (9). Glucocorticoid-induced lymphocytolysis is preceded by cell cycle arrest (28) and extreme morphological changes. These include widespread chromatin condensation, which is associated with extensive DNA fragmentation in both human and murine lymphocytes (22, 58). The DNA cleavage appears to result from the activation of a preexisting calcium-dependent endonuclease (17, 59). Glucocorticoid-induced DNA fragmentation and cell death are prevented when RNA and protein syntheses are inhibited (17). In addition, there is genetic evidence in mouse and human cells for the existence of a locus involved in cell lysis (25,26,63 (21,32,53,62). The possibility thus exists that both glucocorticoids and cAMP regulate the expression of genes involved in the lytic process.Glucocorticoids and cAMP are known to regulate the levels of several proteins in lymphocytes. For example, glucocorticoids induce glucocortin in rat thymus (18), glutamine synthetase in th...