Ontogenetic Development of Rat Intestinal Bile Acid Transport Requires Thyroxine But Not Corticosterone

Abstract

Absorption of bile acids by the distal ileum is an essential component of the enterohepatic circulation. In neonatal rats, the appearance of the apical sodium-dependent bile acid transporter (ASBT) at 17 d of age coincides with increases in serum corticosterone and thyroxine. We tested the hypothesis that these hormones modulate ASBT expression during ileal development. Taurocholate uptake into the isolated ileum of normal 20-d-old pups exhibited saturable (K m ϭ 0.52 mM, J max ϭ 0.34 pmol mg/min) and nonsaturable (K diff ϭ 0.015 min Ϫ1 ) components and was two to five times greater than uptake in the proximal intestine. Hypothyroid or euthyroid pups received daily thyroxine injections starting at 6 d of age. At 12 d of age, serum concentrations of thyroxine, ileal abundance of ASBT mRNA, and ileal rates of taurocholate uptake were low in hypothyroid pups that received an injection of vehicle (HTϪ) or thyroxine (HTϩ) and in euthyroid pups that received an injection of vehicle (ETϪ) or thyroxine (ETϩ). At 20 and 26 d, ileal ASBT mRNA abundance and taurocholate uptake rate remained low in HTϪ pups but increased dramatically in ETϪ and ETϩ pups, paralleling the increase in serum thyroxine. Restoration of normal plasma thyroxine in HTϪ pups by thyroxine injections (HTϩ) restored normal ASBT development. Sodium-glucose co-transporter activity and mRNA expression were independent of serum thyroxine levels. Corticosterone levels were significantly lower in pups that were adrenalectomized at 10 d of age. ASBT mRNA abundance and taurocholate uptake rate increased markedly with age but were the same in adrenalectomized, sham-operated, and nonoperated pups. Hence, endogenous thyroxine but not corticosterone regulates the developmentally timed appearance of ASBT. Bile acids expelled from the gallbladder into the intestinal lumen emulsify dietary lipids to aid digestion, then form micelles with the products of lipid digestion to facilitate absorption. Synthesis of bile acids by the liver is insufficient to meet physiologic needs, and bile acids are recycled in a process that involves their absorption from the intestinal lumen back into the circulation and eventual resecretion from the liver. Bile acids are absorbed passively and in modest amounts in the jejunum (1) but are absorbed actively and in greater amounts in the distal ileum by the apical sodium-dependent transporter (ASBT) located at the brush border membrane of the enterocyte (2). It is not clear when active bile acid absorption begins during ontogenetic development of the small intestine. Sodium-dependent uptake of the bile acid taurocholate has been observed in the small intestine of an 8-mo-old child but not in that of a fetus or a neonate (3). Because reabsorption in the distal small intestine of neonates is inefficient or absent,~10 -20% of fat intake in the formula-fed newborn is thought to be malabsorbed, even though the rate of bile acid synthesis in the neonatal liver is markedly higher than that of older age groups. In rat pups, ASBT mRNA, protein, and ac...

Diet-induced epigenetic regulation in vivo of the intestinal fructose transporter Glut5 during development of rat small intestine

“…GRs translocate from the cytoplasm to the nucleus when ligands such as corticosterone bind to the GR. We have shown previously that plasma glucocorticoid levels in rats were initially low during the suckling stage then increased markedly during weaning [21]. In the present study, we show that GRs translocated from the cytoplasm to the nucleus in the villus of 20-day-old but not 10-day-old rats ( Figure 5).…”

“…Since the GR may regulate Glut5 transcription [13,21], we identified potential GREs (GR response elements) in the Glut5 and Sglt1 promoters, using ALGGEN PROMO (http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi? dirDB = TF_8.…”

“…In vivo approaches to determining mechanisms underlying the unique interaction between ageassociated and sugar-related signals have shown that age-related changes in blood corticosterone levels may control the ability of the dietary signal to up-regulate Glut5 [13,20] because, during rat development, the glucocorticoid hormone increases markedly during the suckling to weaning transition at approx. 14 days of age [21]. Therefore we next hypothesized that Glut5 regulation by age involves signalling via the GR [glucocorticoid receptor; encoded by the Nr3c1 (nuclear receptor subfamily 3 group C member 1) gene].…”

Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC‐QTOF‐MS/MS platform

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Intestinal bile acid physiology and pathophysiology

“…The induction of ABST after birth is stimulated by thyroxine in rats [21] . It is interesting to examine the effects of interference with normal transporter function in the intestine.…”