Sex differences in the mRNA, protein, and functional expression of organic anion transporter (Oat) 1, Oat3, and organic cation transporter (Oct) 2 in rabbit renal proximal tubules

Sex differences in transport of the organic anion (OA) substrate p-aminohippurate (PAH) and the organic cation (OC) substrate tetraethylammonium (TEA) have been recognized for sometime. In the rat kidney, androgens up-regulate and estrogens down-regulate PAH and TEA transport, which correlate with similar changes in mRNA and protein expression for the renal basolateral membrane transporters organic anion transporter (Oat) 1 and organic cation transporter (Oct) 2. However, these sex differences are not readily demonstrated in other species. The present study characterizes the kinetics of basolateral membrane PAH, estrone sulfate (ES), and TEA uptake in renal proximal tubule (RPT) suspensions isolated from female and male rabbits to compare functional expression of transport with mRNA and protein expression for rbOat1, rbOat3, and rbOct2. Although rbOat1-rbOat3 mRNA expression exhibited developmental differences, no sex differences in mRNA levels were observed. Oat1 and Oat3 protein expression in RPT suspensions also was similar between adult female and male rabbits. In contrast, rbOct1 and rbOct2 mRNA levels did not show developmental differences, but rbOct2 mRNA expression was greater in adult male than female rabbits. However, the sex difference in rbOct2 mRNA level did not translate to rbOct2 protein expression. Importantly, functional expression of Oat1, Oat3, and Oct2 transport as measured by kinetics (J_max and K_t) of PAH, ES, and TEA uptake was similar between adult male and female rabbits, and correlated with rbOat1, rbOat3, and rbOct2 protein expression. Thus, unlike rodents, rabbit renal OA and OC transport does not exhibit sex differences, pointing to the need for caution in extrapolating transport-related sex differences between species.