title: Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia.
abstract: 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.
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: S
authors.initials: S
authors.lastname: Faroqui
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
authors.forename: H
authors.initials: H
authors.lastname: Amlal
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000502:physiology*; D017674:Hypophosphatemia / Q000209:etiology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000502:physiology*
chemical_list: D004967:Estrogens; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D004958:Estradiol