β-Estradiol inhibits Na⁺-P_i cotransport across renal brush border membranes from ovarectomized rats

Estrogens play a major role in mineral homeostasis, however it remains unclear whether they exert regulatory action upon reabsorption of phosphate (P_i) in proximal tubules of the kidney. We investigated the effect of β-estradiol (E₂) injected to thyroparathyrodectomized and ovarectomized rats upon Na⁺-cotransport of P_i and other solutes across renal brush border membrane (BBM). In BBM from kidneys of E₂-treated rats the capacity for Na⁺-P_i cotransport was considerably suppressed (Δ% - 42; P < 0.01) whereas Na⁺-cotransports of L-proline D-glucose and SO₄ across the same BBM did not differ from controls. We surmise that E₂ inhibits selectively Na⁺-P_i cotransport by direct interaction with E₂ receptors in proximal tubular cells. These results indicate the existence of the inhibitory effect of estrogens upon renal proximal tubular Na⁺-P_i cotransport and, by extention, proximal Pi reabsorption. We suggest that this modulatory action of E₂ plays a role in pathophysiology of mineral metabolism due to estrogen deficiency and should be considered when estrogens are used for pharmacotherapy of postmenopausal osteoporosis and some types of cancer.