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 (Km = 0.52 mM, Jmax = 0.34 pmol mg/min) and nonsaturable (Kdiff = 0.015 min−1) 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 (HT−) or thyroxine (HT+) and in euthyroid pups that received an injection of vehicle (ET−) or thyroxine (ET+). At 20 and 26 d, ileal ASBT mRNA abundance and taurocholate uptake rate remained low in HT− pups but increased dramatically in ET− and ET+ pups, paralleling the increase in serum thyroxine. Restoration of normal plasma thyroxine in HT− pups by thyroxine injections (HT+) 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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- ADX:
-
adrenalectomized
- ASBT:
-
apical sodium bile acid transporter
- ET−:
-
euthyroid injected with vehicle
- ET+:
-
euthyroid injected with thyroxine
- HT−:
-
hypothyroid injected with vehicle
- HT+:
-
hypothyroid injected with thyroxine
- NOC:
-
nonoperated controls
- SGLT:
-
sodium-dependent glucose transporter
- SHAM:
-
sham-operated
References
Dietschy JM 1974 Bile acids: their absorption from the gastrointestinal tract and role during fat absorption. Verh Dtsch Ges Inn Med 80: 399–407
Love MW, Dawson PA 1998 New insights into bile acid transport. Curr Opin Lipidol 9: 225–229
de Belle RC, Vaupshas V, Vitullo BB, Haber LR, Shaffer E, Mackie GG, Owen H, Little JM, Lester R 1979 Intestinal absorption of bile salts: immature development in the neonate. J Pediatr 94: 472–476
Shneider BL, Setchell KD, Crossman MW 1997 Fetal and neonatal expression of the apical sodium-dependent bile acid transporter in the rat ileum and kidney. Pediatr Res 42: 189–194
Buddington RK, Diamond JM 1989 Ontogenetic development of intestinal nutrient transporters. Annu Rev Physiol 51: 601–619
Cui X, Jiang L, Ferraris RP 2003 Regulation of rat intestinal GLUT2 mRNA abundance by luminal and systemic factors. Biochim Biophys Acta 1612: 178–185
Henning SJ 1987 Functional development of gastrointestinal tract. In: Johnson LR (ed) Physiology of the Gastrointestinal Tract, 2nd Ed., pp 285–300. Raven Press, New York
Henning SJ 1981 Postnatal development: coordination of feeding, digestion, and metabolism. Am J Physiol 241 G199–G214
Little JM, Lester R 1980 Ontogenesis of intestinal bile salt absorption in the neonatal rat. Am J Physiol 239 G319–G323
Barnard JA, Ghishan FK 1986 Methylprednisolone accelerates the ontogeny of sodium-taurocholate cotransport in rat ileal brush border membranes. J Lab Clin Med 108: 549–555
Hwang ST, Henning SJ 2001 Ontogenic regulation of components of ileal bile acid absorption. Exp Biol Med Maywood 226: 674–680
Heubi JE, Gunn TD 1985 The role of glucocorticoids in the postnatal development of ileal active bile salt transport. Pediatr Res 19: 1147–1151
Heubi JE 1986 Role of thyroxine on postnatal development of ileal active bile salt transport. Am J Physiol 251: G237–G242
Shneider BL, Michaud GA, West AB, Suchy FJ 1993 The effects of bile acid feeding on the development of ileal bile acid transport. Pediatr Res 33: 221–224
Stravitz RT, Sanyal AJ, Pandak WM, Vlahcevic ZR, Beets JW, Dawson PA 1997 Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid. Gastroenterology 113: 1599–1608
Monteiro IM, Jiang L, Ferraris RP 1999 Dietary modulation of intestinal fructose transport and GLUT5 mRNA expression in hypothyroid rat pups. J Pediatr Gastroenterol Nutr 29: 563–570
Blake HH, Henning SJ 1985 Effect of propylthiouracil dose on serum thyroxine, growth, and weaning in young rats. Am J Physiol 248: R524–R530
Monteiro IM, Ferraris RP 1997 Precocious enhancement of intestinal fructose uptake by diet in adrenalectomized rat pups. Pediatr Res 41: 353–358
Martin GR, Henning SJ 1984 Enzymic development of the small intestine: are glucocorticoids necessary?. Am J Physiol 246: G695–G699
Karasov WH, Diamond JM 1983 Adaptive regulation of sugar and amino acid transport by vertebrate intestine. Am J Physiol 245:G443–G462
Boehm G, Braun W, Moro G, Minoli I 1997 Bile acid concentrations in serum and duodenal aspirates of healthy preterm infants: effects of gestational and postnatal age. Biol Neonate 71: 207–214
Kanda T, Niot I, Foucaud L, Fujii H, Bernard A, Ono T, Besnard P 1996 Effect of bile on the intestinal bile-acid binding protein (I-BABP) expression. In vitro and in vivo studies. FEBS Lett 384: 131–134
Lewis MC, Root C 1990 In vivo transport kinetics and distribution of taurocholate by rat ileum and jejunum. Am J Physiol 259:G233–G238
Chomczynski P, Sacchi N 1987 Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159
Karasov WH, Diamond JM 1983 A simple method for measuring intestinal solute uptake in vitro. J Comp Physiol 152: 105–116
Takikawa H, Yokote M, Sano N, Kuyama Y, Yamanaka M 1997 Absorption of unconjugated bile acids and tauroursodeoxycholate in the rat intestine. J Gastroenterol Hepatol 12: 815–821
Stelzner M, Hoagland V, Somasundaram S 2000 Distribution of bile acid absorption and bile acid transporter gene message in the hamster ileum. Pflugers Arch 440: 157–162
Shneider BL 2001 Intestinal bile acid transport: biology, physiology, and pathophysiology. J Pediatr Gastroenterol Nutr 32: 407–417
Jiang L, Ferraris RP 2001 Developmental reprogramming of rat GLUT-5 requires de novo mRNA and protein synthesis. Am J Physiol 280: G113–G120
Jiang L, David ES, Espina N, Ferraris RP 2001 GLUT-5 expression in neonatal rats: crypt-villus location and age- dependent regulation. Am J Physiol 281: G666–G674
Walker P, Dubois JD, Dussault JH 1980 Free thyroid hormone concentrations during postnatal development in the rat. Pediatr Res 14: 247–249
Christie DM, Dawson PA, Thevananther S, Shneider BL 1996 Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum. Am J Physiol 271: G377–G385
Paul T, Flatz G 1983 Temporary depression of lactase activity by thyroxine in suckling rats. Enzyme 30: 54–58
Liu T, Reisenauer AM, Castillo RO 1992 Ontogeny of intestinal lactase: posttranslational regulation by thyroxine. Am J Physiol 263: G538–G543
Ardawi MS, Jalalah SM 1991 Effects of hypothyroidism on glucose and glutamine metabolism by the gut of the rat. Clin Sci Lond 81: 347–355
Chang SC, Lin MJ, Croom J, Fan YK 2003 Administration of triiodothyronine and dopamine to broiler chicks increases growth, feed conversion and visceral organ mass. Poult Sci 82: 285–293
Nanthakumar NN, Henning SJ 1993 Ontogeny of sucrase-isomaltase gene expression in rat intestine: responsiveness to glucocorticoids. Am J Physiol 264: G306–G311
Nowicki MJ, Shneider BL, Paul JM, Heubi JE 1997 Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane. Am J Physiol 273: G197–G203
Thomas GB, Bennett PA, Carmignac DF, Robinson IC 2000 Glucocorticoid regulation of growth hormone (GH) secretagogue-induced growth responses and GH secretagogue receptor expression in the rat. Growth Horm IGF Res 10: 45–52
Yeh KY, Yeh M, Holt PR 1987 Hormonal regulation of adaptive intestinal growth in artificially reared rat pups. Am J Physiol 253:G802–G808
Boyle JT, Koldovsky O 1980 Critical role of adrenal glands in precocious increase in jejunal sucrase activity following premature weaning in rats: negligible effect of food intake. J Nutr 110: 169–177
Kaouass M, Deloyer P, Dandrifosse G 1997 Involvement of bombesin in spermine-induced corticosterone secretion and intestinal maturation in suckling rats. J Endocrinol 153: 429–436
Moyer MS, Heubi JE, Goodrich AL, Balistreri WF, Suchy FJ 1986 Ontogeny of bile acid transport in brush border membrane vesicles from rat ileum. Gastroenterology 90: 1188–1196
Wolffram S, Grenacher B, Scharrer E 1993 Intestinal transport of taurocholate in the cat. Zentralbl Veterinarmed A 40: 178–184
Chen F, Ma L, Al-Ansari N, Shneider B 2001 The role of AP-1 in the transcriptional regulation of the rat apical sodium-dependent bile acid transporter. J Biol Chem 276: 38703–38714
Jung D, Fried M, Kullak-Ublick GA 2002 Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha. J Biol Chem 277: 30559–30566
Hwang ST, Urizar NL, Moore DD, Henning SJ 2002 Bile acids regulate the ontogenetic expression of ileal bile acid binding protein in the rat via the farnesoid X receptor. Gastroenterology 122: 1483–1492
Acknowledgements
We are grateful to Ellery Canlas and Lisa Wu for excellent technical help and to Drs. Ben Shneider, Lan Jiang, and Mary Dudley for valuable discussion. We also thank Dr. Shneider for the ASBT cDNA.
Author information
Authors and Affiliations
Additional information
This project was supported by funds from the Foundation of UMDNJ (25-2000 to I.M.M.). Support from NSF Grants IBN-9985808 and IBN-0235011, as well as USDA Grant No. 2001-35102-09881 (to R.P.F.) are also acknowledged.
Rights and permissions
About this article
Cite this article
Monteiro, I., David, E. & Ferraris, R. Ontogenetic Development of Rat Intestinal Bile Acid Transport Requires Thyroxine But Not Corticosterone. Pediatr Res 55, 611–621 (2004). https://doi.org/10.1203/01.PDR.0000112126.07230.9A
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000112126.07230.9A
This article is cited by
-
Bile Acid Transporters: Structure, Function, Regulation and Pathophysiological Implications
Pharmaceutical Research (2007)
