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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Influence of Estrogen and Xenoestrogens on Basolateral Uptake of Tetraethylammonium by Opossum Kidney Cells in Culture

Department of Physiology, University of Arizona, College of Medicine, Tucson, Arizona

The sex steroid hormone estrogen down-regulates renal organic cation (OC) transport in animals, and it 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 (e.g., xenoestrogens) may down-regulate 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 opossum kidney (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, fulvestrant), suggesting that these estrogens regulate OC transport through the estrogen receptor, which was detected (estrogen receptor ) in OK cell cultures by reverse transcription-polymerase chain reaction. The J_max value for TEA uptake in 17-E₂- and DES-treated OK cell cultures was 40 to 50% lower than for ethanol-treated cultures, whereas K_t was unaffected. This reduction in transport capacity was correlated with a reduction in OC transporter OCT1 protein expression following treatment with both agents.

Address correspondence to: Dr. Ryan M. Pelis, Department of Physiology, The University of Arizona, Tucson, AZ 85724. E-mail: rpelis{at}email.arizona.edu