Zonal changes of hepatobiliary taurocholate transport in intrahepatic cholestasis induced by 17α-ethinyl estradiol: A histoautoradiographic study in rats



The liver has a great reserve capacity for hepatobiliary bile salt transport. This study was performed to elucidate the significance of this capacity in ethinyl estradiol–induced cholestasis by direct visualization of the zonal involvement in taurocholate transport. The acinar distribution of [3H]taurocholate was determined by histoautoradiographical study of cryopreserved liver slices in normal rats and rats treated with ethinyl estradiol for 5 days. Silver grain densities over the different acinar zones were estimated on digitized image analysis. In control animals, histoautoradiographical study performed 4 min after the start of perfusion showed restriction of taurocholate to acinar zone 1. In contrast, in ethinyl estradiol–treated animals, taurocholate was also found in zone 2 and, in smaller concentrations, in zone 3. In control animals, the relative blackenings by silver grains of acinar zones 1, 2 and 3 were 66% ± 1.2%, 25% ± 1.6% and 5% ± 0.6%, respectively. After 5 days of ethinyl estradiol treatment, blackenings were 58% ± 1.5%, 36% ± 2.1% and 12% ± 0.8%, respectively. As early as 15 sec after injection of [3H]taurocholate, the bile canalicular areas of the cell plates and the bile ductules of ethinyl estradiol–treated animals were labeled as intensely as those of control animals. Our results demonstrate ethinyl estradiol–induced recruitment of the acinar zones 2 and 3 for hepatobiliary taurocholate transport. This recruitment may largely compensate for reduction of transport capacity of periportal hepatocytes in early cholestasis. (HEPATOLOGY 1993;17:494–499.)