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

Ho Jae Han, Min Jin Lim, Yun Jung Lee, Eun Jung Kim, Young Jin Jeon, Jang Hern Lee

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15 Scopus citations


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-17β (E2) that affects renal proximal tubule cell proliferation and Na+/glucose cotransporters' activity. Thus, the effects of TCDD and E2 on [3H]-thymidine incorporation and on α-methyl-D-glucopyranoside (α-MG) uptake were investigated in the primary rabbit kidney proximal tubule cells (PTCs). TCDD (>10-10 M >1 h) inhibited [3H]-thymidine incorporation and c-fos transcripts in real-time RT-PCR, whereas E2 (>10-9 M, 24 h) stimulated them. Aryl hydrocarbon receptor (AhR) agonists, β-naphthoflavone (β-NF) and polychlorinated biphenyls (PCBs) (10 -6 M) synergistically increased the TCDD-induced inhibition of [ 3H]-thymidine incorporation. However, the AhR antagonist, α-naphthoflavone (α-NF) as well as E2 blocked TCDD-induced inhibition of [3H]-thymidine incorporation. TCDD (10-8 M, 48 h) specifically inhibited α-MG uptake and its effect was due to Vmax value but not Km value. Indeed, TCDD decreased Na+/glucose cotransporter 1, 2 (SGLT1, 2) protein level compared with control. In addition, TCDD-induced inhibition of α-MG uptake was blocked by α-NF or E2. In conclusion, TCDD inhibited [3H]-thymidine incorporation and α-MG uptake, and E 2 blocked TCDDs effects in primary cultured renal proximal tubule cells.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalToxicology in Vitro
Issue number1
StatePublished - Feb 2005

Bibliographical note

Funding Information:
This study was financially supported by Korea Research Foundation (KRF 2003-005-E00012).


  • 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
  • Cell proliferation
  • Estradiol-17β (E )
  • Renal proximal tubule cells (PTCs)
  • α-methyl-D-glucopyranoside (α-MG) uptake


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