Sex steroid modulation of the hepatic uptake of organic anions in rat

Summary To investigate the role of sex steroids in the sex-related difference in the hepatic uptake of organic anions, sulphobromophthalein (bromsulphalein, BSP) transport was measured in hepatocytes isolated from rats either deprived of hormonal influence by castration at prepubertal age or after hormonal substitution. In control animals, the kinetics of BSP uptake showed the presence of two components: one saturable (0–3 μ M), with high affinity and low capacity, and the other linear (9–30 μ M), probably related to the non-specific component of BSP uptake. Sex difference was detected only in the saturable portion of the uptake process as the apparent K m was significantly lower in females than in males (3.8 ± 0.7 vs. 6.1 ± 1.8 μ M, mean ± S.D. of six animals, P V max (2.3 ± 0.3 vs. 2.2 ± 0.7 nmol BSP·(mg protein) −1 ·min −1 . Castration was associated with the disappearance of the saturable uptake site and abolished the sex difference. Progesterone treatment of castrated males failed to restore the saturable kinetics of BSP uptake. In contrast, administration of oestradiol to castrated males or testosterone to castrated females did restore the saturable kinetics of the high-affinity BSP uptake. K m and V max were comparable to those of adult females and males, respectively, with the exception of testosterone which induced a V max value higher than that observed in the other groups of animals. These data suggest that the influence of oestrogen and testosterone is necessary for the expression of the high-affinity, low-capacity carrier-mediated process of hepatic BSP uptake. They also indicate that the sex-related difference in the adult rat is specifically caused by oestrogens.