Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia

Kidney Int. 2008 May;73(10):1141-50. doi: 10.1038/ki.2008.33. Epub 2008 Feb 27.


Estrogen treatment causes significant hypophosphatemia in patients. To determine the mechanisms responsible for this effect, we injected ovariectomized rats with either 17beta-estradiol or vehicle for three days. Significant renal phosphate wasting and hypophosphatemia occurred in estrogen-treated rats despite a decrease in their food intake. The mRNA and protein levels of the renal proximal tubule sodium phosphate cotransporter (NaPi-IIa) were significantly decreased in estradiol-treated ad-libitum or pair-fed groups. Estrogen did not affect NaPi-III or NaPi-IIc expression. In ovariectomized and parathyroidectomized rats, 17beta-estradiol caused a significant decrease in NaPi-IIa mRNA and protein expression compared to vehicle. Estrogen receptor alpha isoform blocker significantly blunted the anorexic effect of 17beta-estradiol but did not affect the downregulation of NaPi-IIa. Our studies show that renal phosphate wasting and hypophosphatemia induced by estrogen are secondary to downregulation of NaPi-IIa in the proximal tubule. These effects are independent of food intake or parathyroid hormone levels and likely not mediated through the activation of estrogen receptor alpha subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Down-Regulation*
  • Estradiol / administration & dosage
  • Estrogens / physiology*
  • Hypophosphatemia / etiology*
  • Kidney Tubules, Proximal / metabolism
  • Phosphates / metabolism*
  • Rats
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / physiology*


  • Estrogens
  • Phosphates
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Estradiol