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J. Biol. Chem., Vol. 265, Issue 26, 15353-15356, Sep, 1990
TL McCarthy, M Centrella and E Canalis
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.
Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast- enriched cultures
Research Laboratory, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.
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