MODULATION OF THE EFFECTS OF GLUCOCORTICOIDS ON COLLAGEN-SYNTHESIS INFETAL-RAT CALVARIAE BY INSULIN-LIKE-GROWTH-FACTOR BINDING PROTEIN-2

To test the hypothesis that insulin-like growth factors (IGFs) play a role in the response of bone to glucocorticoids, we determined the eff ects of cortisol on the incorporation of [H-3]proline into collagenase -digestible protein (CDP) and noncollagen protein (NCP), the percent c ollagen synthesis, and the incorporation of [H-3]thymidine into DNA of 21-day fetal rat calvariae cultured in the presence and absence of re combinant human insulin-like growth factor binding protein-2 (IGFBP-2) . At 24 h, cortisol (100 nM) increased CDP labeling and the percent co llagen synthesis, and these effects were blocked by IGFBP-2 (1000 nM), At 24 h, cortisol decreased the incorporation of [3H] thymidine into bone, which was not affected by the addition of IGFBP-2, At 48 h, cort isol (1000 nM) decreased CDP labeling, which was maintained in the pre sence of IGFBP-2. At 48 h, IGFBP-2 alone decreased basal levels of CDP and NCP labeling and the percent collagen synthesis, Our data suggest that endogenous IGFs maintain basal levels of collagen synthesis and mediate the early stimulatory effect of glucocorticoids on collagen sy nthesis in fetal rat calvariae, However, blocking endogenous IGFs does not abrogate the inhibitory effect of glucocorticoids on DNA synthesi s and the later inhibition of collagen synthesis in calvariae.