Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae.
We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of [3H]proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways.
Kream
B E
BE
Department of Medicine, University of Connecticut Health Center, Farmington 06032.
Petersen
D N
DN
Raisz
L G
LG
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012886:Skull / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D010281:Parathyroid Hormone; D014316:Tritium; D005576:Colforsin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D011392:Proline; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate