Actions of growth factors on plasma calcium. Epidermal growth factor and human transforming growth factor-alpha cause elevation of plasma calcium in mice

J Clin Invest. 1986 Nov;78(5):1405-9. doi: 10.1172/JCI112728.


Specific humoral substances produced and secreted by human tumors that cause hypercalcemia have not been identified. Certain growth factors (such as epidermal growth factor, platelet-derived growth factor, and transforming growth factors-alpha and -beta) have been shown to stimulate the resorption of bone in organ culture by both prostaglandin-dependent and prostaglandin-independent pathways. In this report we demonstrate that epidermal growth factor and recombinant human transforming growth factor-alpha induce a significant rise in plasma calcium concentration when administered repeatedly to intact mice for periods ranging from 24 h to 16 d. The elevation of plasma calcium is not dependent on dietary calcium and is not invariably accompanied by an increase in systemic levels of the prostaglandin E2 metabolite 13,14-dihydro-15-keto-prostaglandin E2. The in vivo calcium-mobilizing activity of epidermal growth factor and transforming growth factor-alpha indicate that these or related growth factors need be considered as potential mediators of tumor-induced hypercalcemia.

Publication types

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

MeSH terms

  • Animals
  • Calcium / blood*
  • Dinoprostone
  • Epidermal Growth Factor / pharmacology*
  • Humans
  • Kinetics
  • Mice
  • Parathyroid Hormone / pharmacology
  • Peptides / pharmacology*
  • Prostaglandins E / blood
  • Transforming Growth Factors


  • Parathyroid Hormone
  • Peptides
  • Prostaglandins E
  • Epidermal Growth Factor
  • Transforming Growth Factors
  • Dinoprostone
  • Calcium