Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone.
PTH stimulates bone resorption and formation, but the mechanism of its anabolic effect is unknown. The effects of PTH on bone formation could be mediated by local regulators, either by altering their binding to receptors or by modulating their synthesis. Cell extracts from PTH-treated osteoblast-enriched cultures isolated from fetal rat parietal bones were examined by Northern blot analysis for changes in mRNAs encoding insulin-like growth factor I (IGF-I), transforming growth factor-beta, and beta 2-microglobulin. PTH did not influence transforming growth factor-beta or beta 2-microglobulin transcript levels. In contrast, PTH-(1-34) had a biphasic stimulatory effect on IGF-I transcript levels; 0.1-10 nM PTH increased IGF-I transcripts by 100-200% after a 6-h treatment, while 100 nM PTH induced a 100% increase. In addition, PTH at 0.01-10 nM increased immunoreactive IGF-I (iIGF-I) in culture medium by 40-200% at 24 h. Maximal increases in IGF-I transcripts occurred at 6 h, while iIGF-I accumulated throughout 24 h of culture. These results are compared to the effects of 0.5-50 nM GH, which increased IGF-I transcripts by 30% and iIGF-I by 50-100%. Therefore, PTH enhanced local IGF-I synthesis by increasing IGF-I transcripts, and this effect may in part mediate the anabolic actions of PTH on bone.
McCarthy
T L
TL
Department of Medicine, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.
Centrella
M
M
Canalis
E
E
D000818:Animals; D001842:Bone and Bones / Q000196:embryology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D015291:Transforming Growth Factors / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics
D015342:DNA Probes; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D013002:Somatomedins; D001613:beta 2-Microglobulin; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D003513:Cycloheximide