Fetal bile salt metabolism. II. Hepatic excretion of endogenous bile salt and of a taurocholate load.

Abstract

Bile salt metabolism was studied in fetal dogs 1 wk before term. The size and distribution of the fetal bile salt pool were measured, and individual bile salts were identified. The hepatic excretion of endogenous bile salts was studied in bile fistula fetuses, and the capacity of this excretory mechanism was investigated by the i.v. infusion of a load of sodium taurocholate-(14)C up to 20 times the endogenous pool size. The total fetal bile salt pool was 30.9+/-2.7 mumoles, of which two-thirds was in the fetal gallbladder. Expressed on a body weight basis, this was equal to approximately one-half the estimated pool size in the adult dog (119.2+/-11.3 vs. 247.5+/-33.1 mumoles/kg body wt). Measurable quantities of bile salt were found in small bowel (6.0+/-1.8 mumoles), large bowel (1.1+/-0.3 mumoles), liver (1.2+/-0.5 mumoles), and plasma (0.1+/-0.03 mumoles). Plasma bile salt levels were significantly greater in fetal than in maternal plasma (1.01+/-0.24 mug/ml vs. 0.36+/-0.06 mug/ml; P < 0.05). Fetal hepatic bile salt excretion showed a fall over the period of study from 2.04+/-0.34 to 0.30+/-0.07 mumoles/hr. The maximal endogenous bile salt concentration in fetal hepatic bile was 18.7+/-1.5 mumoles/ml. The concentration in fetal gallbladder bile was 73.9+/-8.6 mumoles/ml; and, in those studies in which hepatic and gallbladder bile could be compared directly, the gallbladder appeared to concentrate bile four- to fivefold.Taurocholate, taurochenodeoxycholate, and taurodeoxycholate were present in fetal bile, but no free bile salts were identified. The presence of deoxycholate was confirmed by thin-layer chromatography and gas liquid chromatography, and the absence of microorganisms in fetal gut suggests that it was probably transferred from the maternal circulation. After infusion of a taurocholate load, fetal hepatic bile salt excretion increased 30-fold, so that 85-95% of the dose was excreted by the fetal liver during the period of observation. Placental transfer accounted for less than 5% of the dose. Fetal bile volume increased 15-fold on average, while bile salt concentrations increased two- to threefold. It is concluded that bile salt is taken up, conjugated, and excreted by the fetal liver with remarkable efficiency. The excreted material is either stored and concentrated in the fetal gallbladder or released into the intestine and reabsorbed to be reexcreted in bile.