GLUCOCORTICOID REGULATION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN EXPRESSION IN NORMAL HUMAN OSTEOBLAST-LIKE CELLS

Glucocorticoid (GC) modulates insulin-like growth factor (IGF) action in bone through mechanisms that are complex and not well understood. B ecause the family of IGF-binding proteins (IGFBP-1 through -6) is impo rtant in the regulation of IGF availability and bioactivity, we examin ed the effect of GC on IGFBP expression in normal human osteoblast-lik e (hOB) cells. As assessed by Western ligand blot, hOB cells release I GFBP-3, IGFBP-4, and a 31-kilodalton IGFBP, which appeared to be IGFBP -8. Northern analysis revealed that hOB cells express abundant IGFBP-3 , IGFBP-4 IGFBP-5, and IGFBP-6 mRNA, with barely detectable IGFBP-1 mR NA. GC treatment resulted in time- and dose-dependent decreases in IGF BP-3, IGFBP-4, and 31-kilodalton IGFBP levels in culture medium, with corresponding decreases in IGFBP-3, IGFBP-4, and IGFBP-5 mRNA levels. In addition, GC treatment increased steady state levels of IGFBP-1 mRN A and did not alter IGFBP-6 mRNA levels. Although hOB cells secrete an acid-activated IGFBP-3 protease and an IGF-dependent IGFBP-4 protease , GC had little effect on these protease activities and did not alter degradation of the secreted IGFBPs. Our results indicate that GC has d ramatic effects on IGFBP gene expression and suggest that differential regulation of IGFBPs by GC may modulate hOB cell responsiveness to IG Fs.