Estradiol-17beta stimulates phosphate uptake and is mitogenic for primary rabbit renal proximal tubule cells

The direct effects of estradiol-17beta (E(2)) on phosphate (P(i)) uptake and on DNA synthesis in the primary rabbit kidney proximal tubule cells (PTCs) have been investigated. In the present study, E(2) (>10(-9) M, over 9 days) causes an increase both in [(3)H]thymidine incorporation and the number of PTCs. The anti-estrogen tamoxifen completely prevented the E(2)-induced increase in [(3)H]thymidine incorporation, and ameliorated the stimulatory effect of E(2) on growth. E(2) (>10(-9 )M, over 5 days) also stimulated the P(i) uptake and its effect was due to the V(max) values but not to the K(m) value for P(i) uptake. Estriol and estrone also exerted significant stimulatory effects on P(i) uptake. Progesterone, tamoxifen, actinomycin D and cycloheximide prevented the E(2)-induced stimulation of P(i) uptake. In conclusion, estrogens at physiological concentrations stimulate P(i) uptake and DNA synthesis in the renal proximal tubule cells, and these effects are estrogen receptor mediated.