The dimethylsulfoxide (Me2SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10-5 to 10-8 m inhibits by 90-30% and fluocinolone acetonide at concentrations of 10-8 to 10-11 m shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the a- and β-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and that the expression of some of these, in addition to α- and β-globin, is affected by glucocorticoids. The levels of α- and β-globin mRNAs are very close to fully induced levels and preclude transcription as a major site for glucocorticoid control. In addition, it has been shown that glucocorticoids inhibit the translation of α- and β-globin mRNAs, that the level of this inhibition is concentration dependent, and that the translation of β-globin mRNA is slightly more sensitive to inhibition than the translation of α-globin mRNA. It is concluded that, although the translation of α- and β-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of α- and β-globin synthesized. Thus, part of this mechanism may involve a differential sensitivity of α- and β-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.
ASJC Scopus subject areas
- Molecular Biology