Cortisol enhances the expression of mac25 insulin-like growth factor-binding protein-related protein-1 in cultured osteoblasts

Glucocorticoids inhibit the synthesis of insulin-like growth factor I (IGF- I) and regulate the expression of IGF-binding proteins (IGFBPs) in osteobla st cultures. IGFBP-related protein-1 (IGFBP-rP1), the product of the mac25 gene, binds IGF-I, IGF-II, and insulin, and we postulated that glucocortico ids regulate IGFBP-rP1 synthesis in osteoblasts. We tested the expression o f mac25/IGFBP-rP1 in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Cortisol treatment at 10 nM to 1 mu M for 2 4-48 h caused a time- and dose-dependent increase in mac25/IGFBP-rP1 messen ger RNA (mRNA) levels in Ob cells. Cycloheximide at 3.6 mu M did not alter mac25/IGFBP-rP1 transcripts in control or cortisol-treated cells. Cortisol did not modify the decay of mac25/IGFBP-rP1 mRNA in transcriptionally arres ted Ob cells and increased the rate of IGFBP-rP1 transcription as determine d by nuclear run-on assays. Retinoic acid also increased mac25/IGFBP-rP1 mR NA levels, but 17 beta-estradiol, testosterone, 5 alpha-dihydrotestosterone , progesterone, and 1,25-dihydroxyvitamin D-3 did not. In conclusion, corti sol stimulates mac25/IGFBP-rP1 expression in Ob cells by transcriptional me chanisms. As IGFBP-rP1 binds and possibly modifies the effects of IGFs and insulin, its increased Expression could be relevant to the inhibitory actio ns of cortisol in bone.