Aromatase deficient female mice demonstrate altered expression of molecules critical for renal calcium reabsorption

Orhan K. Öz, Asghar Hajibeigi, Carolyn Cummins, Monique Van Abel, René J. Bindels, Makoto Kuro-o, Charles Y C Pak, Joseph E. Zerwekh

Research output: Chapter in Book/Report/Conference proceedingConference contribution


The incidence of kidney stones increases in women after the menopause, suggesting a role for estrogen deficiency. In order to determine if estrogen may be exerting an effect on renal calcium reabsorption, we measured urinary calcium excretion in the aromatase-deficient female mouse (ArKO) before and following estrogen therapy. ArKO mice had hypercalciuria that corrected during estrogen administration. To evaluate the mechanism by which estrogen deficiency leads to hypercalciuria, we examined the expression of several proteins involved in distal tubule renal calcium reabsorption, both at the message and protein levels. Messenger RNA levels of TRPV5, TRPV6, calbindin-D28K, the Na+/Ca- exchanger (NCX1), and the plasma membrane calcium ATPase (PMCA1b) were significantly decreased in kidneys of ArKO mice. On the other hand, klotho mRNA levels were elevated in kidneys of ArKO mice. ArKO renal protein extracts had lower levels of calbindin-D28K but higher levels of the klotho protein. Immunochemistry demonstrated increased klotho expression in ArKO kidneys. Estradiol therapy normalized the expression of TRPV5, calbindin-D28K, PMCA1b and klotho. Taken together, these results demonstrate that estrogen deficiency produced by aromatase inactivation is sufficient to produce a renal leak of calcium and consequent hypercalciuria. This may represent one mechanism leading to the increased incidence of kidney stones following the menopause in women.

Original languageEnglish (US)
Title of host publicationAIP Conference Proceedings
Number of pages5
StatePublished - 2007
Event1st Annual International Urolithiasis Research Symposium - Indianapolis, IN, United States
Duration: Nov 2 2006Nov 3 2006


Other1st Annual International Urolithiasis Research Symposium
CountryUnited States
CityIndianapolis, IN



  • Aromatase
  • Calcium transport proteins
  • Estrogen
  • Kidney
  • Klotho

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Öz, O. K., Hajibeigi, A., Cummins, C., Van Abel, M., Bindels, R. J., Kuro-o, M., Pak, C. Y. C., & Zerwekh, J. E. (2007). Aromatase deficient female mice demonstrate altered expression of molecules critical for renal calcium reabsorption. In AIP Conference Proceedings (Vol. 900, pp. 389-393)