The inhibition of commitment of mouse erythroleukemia cells by steroids involves a glucocorticoid-receptor mediated process(es) acting at the nuclear level.
Dexamethasone has been shown to inhibit dimethylsulfoxide (DMSO)-induced differentiation of mouse erythroleukemia (or Friend) cells by blocking commitment to terminal erythroid maturation. In this study, we confirmed previous reports indicating the presence of glucocorticoid receptors in murine erythroleukemia cells and examined the mechanism(s) by which steroids block commitment. Untreated murine erythroleukemia cells contain dexamethasone receptors which decrease in number during DMSO-induced cell differentiation. When steroids of different classes (estrogenic, androgenic, glucocorticoid) were tested for inhibition of commitment and for displacement of [3H]dexamethasone from its receptors in DMSO-treated cells, we observed that the glucocorticoids dexamethasone, prednisolone and hydrocortisone, all blocked commitment and substantially displaced [3H]dexamethasone. In contrast, steroids other than glucocorticoids failed to inhibit commitment or displace [3H]dexamethasone. Analysis of kinetics of dexamethasone binding to chromatin revealed that dexamethasone binds to the nucleus via the receptor and preferentially interacts with active chromatin. Inhibition of commitment by dexamethasone persisted in cells released from this agent and reincubated with DMSO in the presence of another glucocorticoid of similar affinity to steroid receptors; inhibition of commitment, however, was not obtained when cells removed from dexamethasone were incubated in the presence of beta-estradiol, progesterone and testosterone. These data indicate that inhibition of commitment of mouse erythroleukemia cells by steroids is associated with binding to glucocorticoid receptors and may involve interactions of steroids and their receptors with regions of chromatin.
Tsiftsoglou
A
A
Housman
D
D
Wong
W
W
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D051379:Mice; D008836:Micrococcal Nuclease / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D013256:Steroids; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D011239:Prednisolone; D003850:Deoxyribonuclease I; D008836:Micrococcal Nuclease; D006854:Hydrocortisone; D004121:Dimethyl Sulfoxide