Received for publication June 12, 2007.
Revised August 6, 2007.
Accepted for publication August 6, 2007.

Influence of Estrogen and Xenoestrogens on Basolateral Uptake of TEA by OK Cells in Culture

Abstract

The sex steroid hormone estrogen downregulates renal organic cation (OC) transport in animals and may contribute to sex-related differences in xenobiotic accumulation and excretion. Also, the presence of various endocrine-disrupting chemicals, i.e., environmental chemicals that possess estrogenic activity (i.e., xenoestrogens) may downregulate various transporters involved in renal accumulation and excretion of xenobiotics. The present study characterizes the mechanism by which long-term (6 day) incubation with physiological concentrations of 17-estradiol (E₂) or the xenoestrogens diethylstilbestrol (DES) and bisphenol A (BPA) regulates the basolateral membrane transport of the OC tetraethylammonium (TEA) in OK cell renal cultures. Both 17-E₂ and the xenoestrogen DES produced a dose- and time-dependent inhibition of basolateral TEA uptake in OK cell cultures, whereas the weakly estrogenic BPA had no effect on TEA uptake. Treatment for 6 days with either 1 nM 17-E₂ or DES reduced TEA uptake by ~ 30 and 40 %, respectively. These effects were blocked completely by the estrogen receptor antagonist ICI 182780 (Faslodex®), suggesting that these estrogens regulate OC transport through the estrogen receptor, which was detected (estrogen receptor ) in OK cell cultures by RT-PCR. The J_max for TEA uptake in 17-E₂- and DES-treated OK cell cultures was ~40-50% lower than ethanol-treated cultures while K_t was unaffected. This reduction in transport capacity was correlated with a reduction in OCT1 protein expression following treatment with both agents.

Key words: diethylstilbestrol, estradiol, organic cation, proximal tubule, regulation, tetraethylammonium