Fetal bile salt metabolism: I. The metabolism of sodium cholate-¹⁴C in the fetal dog

Cholate metabolism was studied in fetal dogs 1 wk before term and was compared with cholate metabolism in adult dogs. Tracer amounts of sodium cholate-¹⁴C were administered to the fetus in utero by intravenous infusion over 6 hr. Fetal plasma disappearance, biliary excretion, tissue distribution, and placental transfer of cholate were measured over 10 hr.

Infused cholate-¹⁴C was cleared rapidly from fetal plasma principally by the fetal liver and to a minor extent by placental transfer to the mother. The taurine conjugate was formed in the fetal liver and was excreted into the proximal small intestine via the biliary tree. Indirect evidence for the functioning enterohepatic circulation of bile salt in the fetus was obtained.

Comparison with the results of similar experiments in adult dogs showed that the fetal liver was almost as efficient as the adult liver in the uptake, conjugation, and excretion of tracer amounts of cholate-¹⁴C. The maximal rate of excretion of radiolabel attained by the fetus was somewhat slower than in the adult (82.8 ±1.4% and 96.1 ±4.0% [mean ±SE] of the infusion rate, respectively), and the proportion of the total dose excreted by the fetal liver during 10 hr was smaller (81.4 ±1.3% vs. 96.6 ±4.4%). This difference could be only partly accounted for by placental transfer (2.8 ±0.6% of the fetal dose).

Labeled cholate and taurocholate were excreted by the fetus at similar rates, which suggests that, under the conditions of study, conjugation had little influence on the rate of transfer of cholate across the liver cell.

It is concluded that the fetal dog, 1 wk before birth, has a remarkably mature and efficient mechanism for the uptake and excretion of cholate.

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