Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.
PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.
Canalis
E
E
Department of Medicine (Endocrine Section), Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.
Centrella
M
M
Burch
W
W
McCarthy
T L
TL
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011392:Proline / Q000493:pharmacokinetics; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000493:pharmacokinetics
D010281:Parathyroid Hormone; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011392:Proline; D013936:Thymidine