A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17beta

Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R956-60. doi: 10.1152/ajpregu.00111.2007. Epub 2007 May 30.


Estradiol (E(2)) increases circulating calcium and phosphate levels in fish, thus acting as a hypercalcemic and hyperphosphatemic factor during periods of high calcium requirements, such as during vitellogenesis. Since parathyroid hormone (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we hypothesized that the two hormones could be mediating the same process. Sea bream (Sparus auratus) juveniles receiving a single intraperitoneal injection of piscine PTHrP(1-34) showed an elevation in calcium plasma levels within 24 h. In contrast, injections of the PTH/PTHrP receptor antagonist PTHrP(7-34) decreased circulating levels of calcium in the same period. Intraperitoneal implants of estradiol-17beta (E(2); 10 microg/g) evoked significant increases of circulating plasma levels of calcium and phosphorus and a sustained increases of circulating plasma levels of PTHrP. However, a combined treatment of E(2) and PTHrP(7-34) evoked a markedly lower calcium response compared with E(2) alone. We conclude that PTHrP or a related peptide that binds the PTH/PTHrP receptor mediates, at least in part, the hypercalcemic effect of E(2) in calcium and phosphate balance in fish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / blood
  • Drug Interactions
  • Estradiol / blood
  • Estradiol / pharmacology*
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Hypercalcemia / chemically induced
  • Hypercalcemia / drug therapy*
  • Hypercalcemia / metabolism*
  • Injections, Intraperitoneal
  • Parathyroid Hormone / antagonists & inhibitors*
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone-Related Protein / pharmacology
  • Peptide Fragments / pharmacology
  • Phosphates / blood
  • Proteins / pharmacology
  • Receptor, Parathyroid Hormone, Type 1 / antagonists & inhibitors*
  • Receptor, Parathyroid Hormone, Type 1 / metabolism
  • Sea Bream


  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Phosphates
  • Proteins
  • Receptor, Parathyroid Hormone, Type 1
  • parathyroid hormone-related protein (1-34)
  • parathyroid hormone-related protein (7-34)amide
  • Estradiol
  • Calcium