Parathyroid hormone increases the concentration of insulin-like growth factor-I and transforming growth factor beta 1 in rat bone.

Abstract

Intermittent treatment with parathyroid hormone (PTH) increases bone mass in experimental animals and humans. In vitro studies have suggested that the anabolic effect of PTH may be mediated by local growth factors. However, the relevance of these findings to in vivo situations remains unclear. In this study, we examined a time course of daily s.c. injections of hPTH(1-34) on the skeletal concentration of insulin-like growth factor (IGF)-I, IGF-II, and trans- forming growth factor (TGF-.3) in the proximal tail verte- brae of male rats. PTH caused a time and dose-dependent increase in the bone mineral density of the lumbar spine. This anabolic effect on bone mass was accompanied by pro- gressive increases in bone matrix-associated IGF-I and TGF-fl1. Increases in IGF-I and TGF-1i1 became apparent after four and eight weeks of PTH treatment respectively and persisted through week 12. PTH had no effect on circu- lating IGF-I, suggesting that the increase of bone matrix IGF-I was due to the local effect of PTH on bone tissue directly rather than to an increase of circulating IGF-I. These data are consistent with the hypothesis that IGF-I and TGF-f81 may play a role as local mediators of the ana- bolic effects of PTH on bone metabolism. (J. Clin. Invest.