Physiological concentrations of 17β‐estradiol downregulate organic cation (OC) transport in the opossum kidney (OK) cell line

In rats administration of 17‐βEstradiol (17β‐E 2 ) downregulates renal slice OC transport, but the mechanism of this downregulation has not been characterized. A decrease in transport may be accomplished by changing the capacity (J max ) or affinity (K m ) of substrate for a transporter. The objective of this study was to characterize the effect of long‐term (6 day) exposure to 17β −E 2 on the kinetics of basolateral membrane transport of tetraethylammonium (TEA) in OK cell cultures. Six‐day treatment of OK cell cultures with 10 to 1000 nM 17β −E 2 decreased TEA transport ~40–50% compared to control. The regulation of OC transport by treatment with 10 nM 17β −E 2 was further characterized by measuring the kinetics of basolateral TEA uptake in OK cell cultures. The capacity for TEA uptake in OK cell cultures decreased ~ 45% (ethanol‐treated vs. 17β‐E 2 ‐treated, J max = 38 ± 5 mol.cm −2. min −1 vs. 21 ± 1.4 mol.cm −2 min −1 ), whereas no significant change in the affinity for basolateral TEA uptake was observed between control and 17β‐E 2 treated cultures (ethanol‐treated vs. 17β‐E 2 ‐treated, K m = 24 ± 4 vs. 19 ± 1 μM). The significant decrease in the J max for basolateral TEA uptake with no change in K m suggests a downregulation of OC transport protein levels. Thus, our data suggest that long‐term exposure to physiological concentrations of 17β‐E 2 may downregulate TEA transport by a decrease in OC transporter protein expression. ( DK062097 )