Parathyroid hormone stimulates release of insulin-like growth factor-I (IGF-I) and IGF-II from neonatal mouse calvaria in organ culture.
Effects of increased bone resorption on release of insulin-like growth factor-I (IGF-I) and IGF-II into the osteoblast microenvironment were investigated using neonatal mouse calvaria organ cultures. Release of these growth factors from calvaria into serum-free medium was quantitated using a human IGF-I RIA and human IGF-II RRA. Untreated calvaria released several-fold more IGF-II than IGF-I. PTH (from 1-12 nM) stimulated a dose-dependent increase in the release of both growth factors that correlated with increased calcium release and was sustained for up to 6 days. IGF-I and IGF-II release were maximally stimulated 5- to 10-fold and 1.5- to 2-fold, respectively, compared to untreated control values. Calcitonin inhibited PTH-stimulated resorption, but had no effect on PTH stimulation of IGF-I and IGF-II release, suggesting that PTH effects on IGF-I and IGF-II release were not dependent on resorption. Furthermore, the amounts of IGF-I and IGF-II released from calvaria during 6 days of culture were 5-fold more than the amounts of IGF-I and IGF-II present in the calvaria (bone plus cells) at the beginning of culture, suggesting that much of the IGF-I and IGF-II released was newly produced by calvaria cells. The results suggest that PTH directly stimulated calvarial osteoblasts to release IGF-I and IGF-II. Since IGF-I and IGF-II stimulate osteoblastic cell proliferation, the effect of PTH on the release of these and other growth factors may mediate coupling of bone formation to bone resorption.
Linkhart
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Department of Biochemistry, Loma Linda University School of Medicine, Veterans' Hospital, Loma Linda, California 92357.
Mohan
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D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011863:Radioimmunoassay; D013002:Somatomedins / Q000378:metabolism*; D013997:Time Factors
D010281:Parathyroid Hormone; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II