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.
Department of Biochemistry, Loma Linda University School of Medicine, Veterans' Hospital, Loma Linda, California 92357.
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Linkhart
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Mohan
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