| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
LIVER AND BILIARY TRACT
Laboratory of Developmental and Molecular Hepatology, Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
Submitted 3 August 2004 ; accepted in final form 20 September 2004
Nuclear receptors (NRs) play pivotal roles in the regulation of genes contributing to hepatobiliary cholesterol and bile acid homeostasis. We have previously shown that transporters involved in bile formation are developmentally regulated and are poorly developed during the fetal stage, but their expression reached gradual maturity during the postnatal period. To define the molecular mechanisms underlying this regulation and the role that class II NRs and associated members [liver receptor homolog-1 (LRH-1) and short heterodimer partner (SHP)] play, we have analyzed the ontogeny of NR expression during liver development. Real-time PCR analysis of hepatic NR expression from fetal day 17 through adult revealed that steady-state mRNA levels for all NRs were very low during the embryonic period. However, mRNA levels peaked close to that of adult rats (>6 wk-old rats) by 4 wk of age for farnesoid X receptor (FXR), pregnane X receptor (PXR), liver X receptor-
(LXR), peroxisome proliferator-activated receptor- (PPAR), retinoid acid receptor- (RAR), LRH-1, and SHP, whereas RXR mRNA lagged behind. FXR, PXR, LXR, RAR, and PPAR functional activity in liver nuclear extracts assayed by gel EMSA demonstrated that the activity attained adult levels by 4 wk of age, exhibiting a strict correlation with mRNA levels. Surprisingly, PPAR activity was delayed as seen by EMSA assay. Protein levels for NRs also corresponded to the mRNA and functional activity except for RXR. RXR protein levels were higher than message levels, suggesting increased protein stability. We conclude that expression of NRs during rat liver development is primarily regulated by transcriptional mechanisms, which in turn, control the regulation of bile acid and cholesterol metabolic pathways.
ontogeny; bile acids; cholesterol
This article has been cited by other articles:
|
|
 |
|
  E. M. E. van Straten, N. C. A. Huijkman, J. F. W. Baller, F. Kuipers, and T. Plosch Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1341 - E1348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Geier, I. V. Martin, C. G. Dietrich, N. Balasubramaniyan, S. Strauch, F. J. Suchy, C. Gartung, C. Trautwein, and M. Ananthanarayanan Hepatocyte nuclear factor-4{alpha} is a central transactivator of the mouse Ntcp gene Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G226 - G233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ballatori, F. Fang, W. V. Christian, N. Li, and C. L. Hammond Ost{alpha}-Ost{beta} is required for bile acid and conjugated steroid disposition in the intestine, kidney, and liver Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G179 - G186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sakamoto, T. Kawasaki, T. Kazawa, R. Ohashi, S. Jiang, T. Maejima, T. Tanaka, H. Iwanari, T. Hamakubo, J. Sakai, et al. Expression of Liver X Receptor {alpha} in Rat Fetal Tissues at Different Developmental Stages J. Histochem. Cytochem., June 1, 2007; 55(6): 641 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A Maloney and W. D Rees Gene-nutrient interactions during fetal development Reproduction, October 1, 2005; 130(4): 401 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-X. Xu, Y.-H. Chen, J.-P. Wang, M.-F. Sun, H. Wang, L.-Z. Wei, and W. Wei Perinatal Lipopolysaccharide Exposure Downregulates Pregnane X Receptor and Cyp3a11 Expression in Fetal Mouse Liver Toxicol. Sci., September 1, 2005; 87(1): 38 - 45. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
