Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia.
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.
Faroqui
S
S
Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Levi
M
M
Soleimani
M
M
Amlal
H
H
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*
D004967:Estrogens; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D004958:Estradiol