515 SERUM BILE ACIDS REFLECT THE DEVELOPMENT OF THE ENTEROHEPATIC CIRCULATION IN RATS

Abstract

We have shown that serum bile acid concentrations are elevated during early life in humans reflecting physiologic immaturity of the enterohepatic circulation. To further define the ontogeny of bile acid metabolism in mammals, we sought maturational changes in the serum values of total cholyl conjugates via a sensitive, specific radioimmunoassay in fetal, suckling, and mature Sprague-Dawley rats.Results: Fetal (21st day) bile acid levels were low (1.42 ± 0.23* μM; x ± SEM) probably due to minimal enterohepatic cycling in utero. With initial suckling, levels rose rapidly (9.27 ± 1.57* on day 1), remained elevated on day 4 (9.63 ± 0.73*), and fell briefly but significantly on day 7 (6.36 ± 0.68, p<0.001 vs day 4). Subsequent elevations were attained stepwise throughout the suckling phase (day 10=7.24 ± 0.57*; day 14=10.47 ± 1.70*, day 21=16.81 ± 1.93*). Following weaning there was a dramatic peak on day 28 (21.76 ± 1.53*); values then fell (5.57 ± 0.68 on day 42) to achieve adult normals by 56 days.Conclusion: Serum bile acid levels reflect sequential developmental maturation of the enterohepatic circulation in the rat. These changes corroborate previous data citing underdeveloped bile canalicular morphology at birth, maturation of intestinal reabsorption, increasing postnatal pool size.before day 56, and persistently impaired hepatic function during normal development. Further studies are warranted to define modulating influences responsible for perinatal physiological and possibly pathophysiological changes in hepatic and intestinal bile acid transport.*p<0.001 vs adult (3.97 ± 0.55 @ 56 day)