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Although several studies have demonstrated an inverse relationship between size of the bile salt pool and frequency of enterohepatic cycling, most such data have been obtained in conditions where control of cycling frequency was not possible. In this study, we diverted bile from the bile duct of Rhesus monkeys into a reservoir and returned it to the duodenum at varying rates, a model that mimicked differences in frequency of gallbladder emptying. As cycling frequency increased from 1 to 8 cycles/day, size of the bile salt pool decreased from 1756 microM to 369 microM. Changes in fractional turnover rate parallelled changes in cycling frequency. The relative composition of the biliary lipids remained the same throughout the range of cycling frequencies. These data show that direct manipulation of cycling frequency had the predicted effects on other parameters of the enterohepatic circulation but did not give rise to lithogenic bile.

The effects of cholecystectomy upon bile salt kinetics were studied in normal guinea pigs. After cholecystectomy, bile salt pool size decreased, fractional daily turnover rate increased, and the rate of bile salt synthesis was unchanged. These data indicate that an increased frequency of bile salt enterohepatic cycling is sufficient to produce alterations in bile salt kinetics. Abnormalities of bile salt synthesis need not be present in order for a reduction in pool size to occur.

Metabolism of the bile salts by formation of sulfate esters is catalyzed by bile salt sulfotransferase, an enzyme isolated from rat liver and kidney. The activity of bile salt sulfotransferase was measured in liver and kidney of male and female rats and in oophorectomized rats with or without estrogen replacement. In vitro sulfotransferase activity was correlated with in vivo sulfation by measuring the percentage of an infused dose (0.03 micron per 100 g per min) of taurolithocholate, which was excreted in bile as the sulfate. The activity of sulfotransferase in liver was higher in females (26.3 +/- 3.0 pmoles per mg of protein per min) than in males (9.6 +/- 3.9) and was lower (12.1 +/- 3.8) after oophorectomy. The decrease in activity was prevented by replacement of estrogen. Renal sulfotransferase activity did not differ between the sexes and was unaffected by oophorectomy. Hepatic sulfotransferase activity measured in vitro correlated with in vivo sulfation of taurolithocholate. This study shows definite sex differences in hepatic bile salt sulfotransferase activity, which in females is affected by the presence of estrogen. The correlation between in vitro sulfotransferase activity and in vivo bile salt sulfation suggests that bile salt sulfotransferase is responsible for bile salt sulfation in vivo.