Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone

TL Mccarthy, M Centrella, E CANALIS - Endocrinology, 1989 - academic.oup.com
TL Mccarthy, M Centrella, E CANALIS
Endocrinology, 1989academic.oup.com
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-β, and β2-microglobulin. PTH did not influence …
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-β, and β2-microglobulin. PTH did not influence transforming growth factor-β or β2-microglobulin transcript levels. In contrast, PTH-(1-34) had a biphasic stimulatory effect on IGFI 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. (Endocrinology124: 1247- 1253, 1989)
Oxford University Press