CORTISOL REPRESSES INSULIN-LIKE GROWTH-FACTOR-II RECEPTOR TRANSCRIPTION IN SKELETAL CELL-CULTURES

Glucocorticoids have a number of effects on bone cell function, some o f which might be mediated by changes in the synthesis or activity of i nsulin-like growth factors (IGFs). Glucocorticoids inhibit IGF-I, but not IGF-II, synthesis in osteoblasts and decrease the expression of se lected IGF-binding proteins. The effects of glucocorticoids on IGF-I a nd -II receptor messenger RNA (mRNA) expression in osteoblasts are not known, and changes in IGF-I or -II receptor levels could result in ch anges in IGF activity. We examined the effects of glucocorticoids on I GF-I and -II receptor mRNA expression in cultures of osteoblast-enrich ed cells from 22-day-old fetal rat calvariae (Ob cells). Cortisol at 1 mu M for 2-48 h did not alter IGF-I receptor transcripts, as determin ed by Northern blot analysis and ribonuclease protection assay. In con trast, cortisol caused a time- and dose-dependent inhibition of IGF-II receptor mRNA levels. The effect was maximal at 0.1-1 mu M for 24-48 h and was accompanied by a decrease in IGF-II receptor levels, as dete rmined by affinity labeling, cross-linking and polyacrylamide gel elec trophoresis, Western immunoblot, and Scatchard analysis. The effect of cortisol on IGF-II receptor transcripts was not dependent on de novo protein synthesis. Cortisol did not modify the IGF-II receptor mRNA ha lf-life in transcriptionally arrested Ob cells and decreased the rate of IGF-II receptor RNA transcription in nuclear run-on assays. In conc lusion, cortisol decreases transcription of the TGF-II receptor in Ob cell cultures, an effect that could mediate selected actions of glucoc orticoids in bone.