Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures.
Glucocorticoids have a number of effects on bone cell function, some of which might be mediated by changes in the synthesis or activity of insulin-like growth factors (IGFs). Glucocorticoids inhibit IGF-I, but not IGF-II, synthesis in osteoblasts and decrease the expression of selected IGF-binding proteins. The effects of glucocorticoids on IGF-I and -II receptor messenger RNA (mRNA) expression in osteoblasts are not known, and changes in IGF-I or -II receptor levels could result in changes in IGF activity. We examined the effects of glucocorticoids on IGF-I and -II receptor mRNA expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Cortisol at 1 microM for 2-48 h did not alter IGF-I receptor transcripts, as determined by Northern blot analysis and ribonuclease protection assay. In contrast, cortisol caused a time- and dose-dependent inhibition of IGF-II receptor mRNA levels. The effect was maximal at 0.1-1 microM for 24-48 h and was accompanied by a decrease in IGF-II receptor levels, as determined by affinity labeling, cross-linking and polyacrylamide gel electrophoresis, 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 half-life in transcriptionally arrested Ob cells and decreased the rate of IGF-II receptor RNA transcription in nuclear run-on assays. In conclusion, cortisol decreases transcription of the IGF-II receptor in Ob cell cultures, an effect that could mediate selected actions of glucocorticoids in bone.
Rydziel
S
S
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Canalis
E
E
D000818:Animals; D002478:Cells, Cultured; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006854:Hydrocortisone