Effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: role of insulin-like growth factor-I

Endocrinology. 1993 Oct;133(4):1504-10. doi: 10.1210/endo.133.4.7691577.


Prostaglandin E2 (PGE2) can stimulate collagen synthesis in bone at low concentrations or in the presence of cortisol. Moreover, cortisol inhibits and PGE2 stimulates the production of insulin-like growth factor (IGF-I) in cultured osteoblastic cells. Therefore, we examined the role of IGF-I in the response to PGE2. In 96-h fetal rat calvarial organ cultures, PGE2 increased, and cortisol and indomethacin decreased the medium IGF-I concentration, suggesting that both exogenous and endogenous PGs regulate IGF-I production. In the presence of cortisol, the stimulatory effects of PGE2 on medium IGF-I and incorporation of [3H] proline into collagenase-digestible protein were highly correlated (r = 0.95). When exogenous IGF-I (30 nM) was added, the stimulatory effect of PGE2 was abrogated in the absence, but not the presence, of cortisol. When we added IGF-binding proteins, which blocked the effects of IGF-I and IGF-II, collagenase-digestible protein labeling was decreased in control and cortisol-treated cultures, whereas the stimulatory effect of PGE2 was reduced, but not abrogated. We conclude that endogenous IGFs play a role in maintaining bone formation in cultured fetal rat calvariae and may mediate in part the anabolic response to PGE2. However, the PGE2 response probably involves additional IGF-independent pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / pharmacology
  • Cells, Cultured
  • Collagenases
  • Culture Techniques
  • Dinoprostone / pharmacology*
  • Fetus / metabolism
  • Fetus / physiology*
  • Growth Inhibitors / pharmacology
  • Hydrocortisone / pharmacology
  • Indomethacin / pharmacology
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / physiology*
  • Osteogenesis / drug effects*
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Skull / embryology
  • Skull / growth & development*
  • Thymidine / pharmacokinetics


  • Carrier Proteins
  • Growth Inhibitors
  • Insulin-Like Growth Factor Binding Proteins
  • Proteins
  • Insulin-Like Growth Factor I
  • Collagenases
  • Dinoprostone
  • Thymidine
  • Hydrocortisone
  • Indomethacin