S. Rydziel et E. Canalis, CORTISOL REPRESSES INSULIN-LIKE GROWTH-FACTOR-II RECEPTOR TRANSCRIPTION IN SKELETAL CELL-CULTURES, Endocrinology, 136(10), 1995, pp. 4254-4260
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.