Effects of TCDD and estradiol-17β on the proliferation and Na+/glucose cotransporter in renal proximal tubule cells

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental toxicant that alters cell proliferation and function. Estrogens are noted for their ability to stimulate cell proliferation in various tissues. However, little is known about any interaction between TCDD and estradiol-17beta (E-2) that affects renal proximal tubule cell proliferation and Na+/glucose cotransporters' activity. Thus, the effects of TCDD and E-2 on [H-3]-thymidine incorporation and on alpha-methyl-D-glucopyranoside (alpha-MG) uptake were investigated in the primary rabbit kidney proximal tubule cells (PTCs). TCDD (>10(-10) M >1 h) inhibited [H-3]-thymidine incorporation and c-fos transcripts in real-time RT-PCR, whereas E-2 (>10(-9) M, 24 h) stimulated them. Aryl hydrocarbon receptor (AhR) agonists, beta-naphthoflavone (beta-NF) and polychlorinated biphenyls (PCBs) (10(-6) M) synergistically increased the TCDD-induced inhibition of [H-3]-thymidine incorporation. However, the AhR antagonist, alpha-naphthoflavone (alpha-NF) as well as E2 blocked TCDD-induced inhibition of [H-3]-thymidine incorporation. TCDD (10(-8) M, 48 h) specifically inhibited alpha-MG uptake and its effect was due to V-max value but not Kn, value. Indeed, TCDD decreased Na+/glucose cotransporter 1, 2 (SGLT1, 2) protein level compared with control. In addition, TCDD-induced inhibition of alpha-MG uptake was blocked by alpha-NF or E-2. In conclusion, TCDD inhibited [H-3]thymidine incorporation and alpha-MG uptake, and E-2 blocked TCDDs effects in primary cultured renal proximal tubule cells. (C) 2004 Elsevier Ltd. All rights reserved.