Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures

Earlier studies indicate that parathyroid hormone (PTH) enhances insulin-like growth factor I (IGF-I) synthesis in primary osteoblast-enriched fetal rat cell cultures and the stimulatory effect of PTH on bone collagen synthesis is mediated at least in part by IGF-I. Cyclic AMP (cAMP) is a second messenger for signal transduction by PTH to its target cells, although calcium may also serve this function. We now demonstrate that isobutylmethylxanthine, forskolin, and dibutyryl cAMP, agents that elevate intracellular cAMP levels by discrete mechanisms, also enhanced the steady state transcript and polypeptide level of IGF-I in osteoblast-enriched cultures. The calcium ionophore ionomycin and phorbol myristate acetate did not increase IGF-I synthesis. In contrast, none of the agents tested increased the steady state transcript or polypeptide levels for IGF-II. The rat IGF-I gene is greater than 90 kilobases in length, and contains at least three promoter regions. Our present data represent the first demonstration of cAMP mediated IGF-I gene regulation and indicate the potential for preferential promoter usage for modulating IGF-I gene expression in bone.