Estradiol-17β Stimulates Phosphate Uptake and Is Mitogenic for Primary Rabbit Renal Proximal Tubule Cells

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Abstract
The direct effects of estradiol-17β (E2) on phosphate (Pi) uptake and on DNA synthesis in the primary rabbit kidney proximal tubule cells (PTCs) have been investigated. In the present study, E2 (>10–9M, over 9 days) causes an increase both in [3H]thymidine incorporation and the number of PTCs. The anti-estrogen tamoxifen completely prevented the E2-induced increase in [3H]thymidine incorporation, and ameliorated the stimulatory effect of E2 on growth. E2 (>10–9 M, over 5 days) also stimulated the Pi uptake and its effect was due to the Vmax values but not to the Km value for Pi uptake. Estriol and estrone also exerted significant stimulatory effects on Pi uptake. Progesterone, tamoxifen, actinomycin D and cycloheximide prevented the E2-induced stimulation of Pi uptake. In conclusion, estrogens at physiological concentrations stimulate Pi uptake and DNA synthesis in the renal proximal tubule cells, and these effects are estrogen receptor mediated.