help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Feng, X.
Right arrow Articles by Yen, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feng, X.
Right arrow Articles by Yen, P. M.
Molecular Endocrinology 14 (7):947
Copyright © 2000 by The Endocrine Society

Thyroid Hormone Regulation of Hepatic Genes in Vivo Detected by Complementary DNA Microarray

Xu Feng, Yuan Jiang, Paul Meltzer and Paul M. Yen

Molecular Regulation and Neuroendocrinology Section Clinical Endocrinology Branch (X.F., P.M.Y.) National Institute of Diabetes and Digestive and Kidney Diseases
Cancer Genetics Branch (Y.J., P.M.) National Human Genome Research Institute National Institutes of Health Bethesda, Maryland 20892


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESULTS AND DISCUSSION
 MATERIALS AND METHODS
 The European Journal of...
 REFERENCES
 
The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression in vivo and should prove to be a powerful tool for future studies of hormone and drug action.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESULTS AND DISCUSSION
 MATERIALS AND METHODS
 The European Journal of...
 REFERENCES
 
Thyroid hormones (T3 and T4) have profound effects on metabolism, growth, and development (1 ). The effects of thyroid hormone are mediated by thyroid hormone receptors (TRs) that belong to the nuclear hormone receptor superfamily; these include the steroid hormone receptors, the retinoic acid receptors, the retinoid X receptors , the vitamin D receptor, the peroxisome proliferator-activated receptors, and other orphan receptors (2 3 ). TRs are encoded by two genes ({alpha} and ß) and are expressed as several isoforms (TR{alpha}, TRß1, and TRß2) (2 3 ). TRs bind to thyroid hormone-response elements in the promoters of target genes. Interestingly, T3 can positively and negatively regulate transcription of target genes (2 3 4 ); however, only a few of the approximately 30 known target genes are negatively regulated. Moreover, most of these negatively regulated target genes are expressed in the pituitary or hypothalamus (2 3 4 ) rather than peripheral tissues.

The liver is a major target organ of thyroid hormone. It has been estimated that approximately 8% of the hepatic genes are regulated by thyroid hormone in vivo (1 ), and thus the liver is an ideal tissue to study gene regulation by thyroid hormone. Although a limited number of individual target genes in the liver have been studied, a large-scale profile of the target genes regulated by thyroid hormone has not been undertaken. cDNA microarray hybridization is a powerful tool to study hormone effects on cellular metabolism and gene regulation on a genomic scale as it enables simultaneous measurement and comparison of the expression levels of thousands of genes (5 6 ). Recently, cDNA microarrays have been used to study the gene expression due to fibroblast differentiation; oncogenesis; aging and caloric restriction of mouse muscle; cell cycle in yeast; and differentiation in Drosophila (7 8 9 10 11 12 13 ). They also have been used in drug development programs to monitor changes in gene expression due to drug treatment (14 ). Additionally, two groups recently have used microarrays to examine broad patterns of gene regulation in leukemias and lymphomas and correlate the pattern with clinical outcome (15 16 ). Thus far, microarrays have not been used to assess hormonal regulation of target genes and their patterns of expression.

We have used a cDNA microarray to study the hepatic gene expression in hypothyroid mice treated with T3. We have identified 55 target genes, with 14 up-regulated and 41 down-regulated by T3. Most of these genes have not previously been described to be regulated by thyroid hormone. Analyses of their expression profile revealed thyroid hormone effects on multiple cellular pathways. This study also is the first application of cDNA microarray technology to study hormonal regulation of target genes in vivo.


   RESULTS AND DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS AND DISCUSSION
MATERIALS AND METHODS
 The European Journal of...
 REFERENCES
 
Microarray Analyses
To investigate the effect of thyroid hormone on hepatic gene expression, RNA from hypothyroid and T3-treated mice was prepared, labeled with fluorescent dye, and hybridized with the cDNA microarray as described in Materials and Methods. The color images of the hybridization results (Fig. 1Go) were made by representing the Cy3 fluorescent image as green and Cy5 fluorescent image as red, and merging the two color images. Similar findings were observed in a total of six independent microarray studies of livers from individual mice treated with T3 or T4.



View larger version (15K):
[in this window]
[in a new window]
  		Figure 1. A Representative Portion of the Microarray Used to Detect Hepatic Genes Regulated by T3

A microarray was hybridized to total RNA from hypothyroid mouse liver (green fluorochrome) and hyperthyroid mouse liver after 6 h treatment with thyroid hormone (red fluorochrome). RNA from the hypothyroid mouse liver was used to prepare cDNA labeled with Cy3-deoxyuridine triphosphate (dUTP), and mRNA hyperthyroid mouse liver was used to prepare cDNA labeled with Cy5-dUTP. The two cDNA probes were mixed and then simultaneously hybridized to the microarray. In this image of the subsequent scan, mRNAs that were more abundant in hypothyroid mouse liver (suppressed by thyroid hormone) were detected as green spots, whereas mRNAs that were more abundant in hyperthyroid mouse liver (stimulated by thyroid hormone) were detected as red spots. Yellow spots represented genes whose expression did not vary substantially between the two samples. The arrows indicate spots representing the following genes: 1. Bcl-3; 2. carbonyl reductase; 3. B61; 4. membrane-type matrix metalloproteinase; 5. Spot 14.

 
We sampled 2225 genes on the cDNA microarray, which represents approximately 10% of the expressed genes in liver, assuming that the liver transcriptosome contains 10,000–20,000 genes (20 ). We found that 14 genes (0.6%) displayed a greater than 2-fold increase in expression levels after thyroid hormone treatment whereas 41 genes (2.4%) displayed more than a 60% decrease in gene expression (Table 1Go). This latter finding was surprising since there are only a few known negatively regulated target genes in peripheral tissues. Seven of 14 of the positively regulated genes were not identified previously as thyroid hormone-responsive, whereas 38/41 of the negatively regulated genes were not identified previously as such. Three genes (malic enzyme, {alpha} myosin heavy chain, and myelin basic protein) have been described previously to be regulated by T3 but did not show significant induction in our studies even though they were contained on the microarray. The latter two genes are predominantly expressed in heart and brain, respectively, and not significantly expressed in liver (19 ). Weiss et al. (17 ) recently treated a different strain of mice for 4 days with T3 and observed induction of malic enzyme mRNA (17 ). The observed lack of T3-induction of malic enzyme mRNA may be due to delayed time course of induction (6 h vs. 4 days) or differences in mouse strains.


View this table:
[in this window]
[in a new window]
  		Table 1. List of Hepatic Genes Regulated by T3 Determined by cDNA Microarray Analyses

 
The changes in mRNA levels of several known and novel target genes on the microarray were confirmed by Northern blot analysis (Fig. 2Go). Our data are consistent with previous studies that have shown that cDNA microarrays can predict induction and repression of gene expression on Northern blots with high reliability (7 10 ). The major factors affecting the reliability of microarray analyses are the quality of RNA and the efficiency of labeling. Therefore, hybridization and microarray analyses were only performed in samples in which high specific labeling of RNA was achieved. Only genes that were regulated in three separate experiments comparing mice treated with propylthiouracil (PTU) ± T3 are included in Table 1Go. These results also were confirmed in three additional experiments in which mice were treated with PTU ± T4.



View larger version (67K):
[in this window]
[in a new window]
  		Figure 2. Autoradiograph of Northern Blots Containing Total RNA (20 µg) from Hypothyroid Mice (C) and Hyperthyroid Mice (T) That Were Probed with cDNA from Genes That Were Regulated by T3 on Microarray

Molecular weights of the hybridizing bands were consistent with published transcript sizes. The control signals of 36B4 showed that similar amounts of RNA samples were loaded.

 
Consistent with some of the known metabolic effects of thyroid hormone, T3 regulated a diverse range of genes that affect many different aspects of cellular metabolism and function such as gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis (Table 1Go and Fig. 3Go).



View larger version (13K):
[in this window]
[in a new window]
  		Figure 3. Cellular Pathways and Functions Detected by cDNA Microarray That Are Regulated by Thyroid Hormone

 
Gene Profiles and Novel Target Genes Regulated by T3
T3 stimulates gluconeogenesis and glucose production in the liver and thus opposes the action of insulin with respect to hepatic glucose production (21 22 ). It also is known that hyperthyroidism worsens glycemic control in diabetic patients (23 24 ). In accord with these findings, we found an increase in glucose-6-phosphatase mRNA expression, the key enzyme for conversion of glucose-6-phosphate to glucose. Additionally, we observed a decrease in mRNA expression of a critical downstream component of the insulin-signaling pathway, Akt2 (protein kinase B). Akt2 is a serine/threonine kinase that is activated by insulin and other growth factors via phosphatidylinositol 3 kinase (25 26 ). Akt2 has been shown to stimulate glucose uptake in peripheral tissues via GLUT 4 glucose transporter and to promote glycogen synthesis in liver by inactivating glycogen synthase kinase 3 (27 28 29 ). Thus, a decrease in Akt2 activity would decrease glycogen synthesis. It also is interesting that T3 decreased capping protein {alpha} subunit and {alpha} adaptin mRNA which encode proteins that are involved in the redistribution and internalization of the liganded insulin receptor (30 31 ). In this connection, it recently was reported that there is decreased endocytosis of insulin receptors in hepatocytes of diabetic rats (32 ). T3 also increased insulin-like growth factor (IGF) binding protein-1 mRNA, which inhibits IGF-I signaling as reported previously (33 ).

It previously has been shown that thyroid hormone can mimic or enhance the glycogenolytic and gluconeogenic effects of epinephrine and glucagon in hepatocytes, and increase intracellular cAMP (21 34 35 36 ). Consistent with these findings, we observed induction of ß2-adrenergic receptor mRNA and repression of inhibitory G protein (Gi) mRNA of the adenylate cyclase cascade (Table 1Go). Thus, T3 has complementary effects on two opposing pathways that regulate intracellular cAMP. Additionally, T3 may have other effects on this signaling cascade as T3 has been reported to redistribute Gs{alpha} from cytosol to the plasma membrane, up-regulate Gs{alpha}, and down-regulate Gi{alpha} expression in the plasma membrane, as well as modulate the activity of phosphodiesterase (37 38 ).

Hepatic lipogenesis is regulated by dietary substrates and hormones such as insulin and thyroid hormone, which control fuel metabolism and biosynthesis (1 ). We observed increased mRNA expression of spot 14 (S14), a key protein that regulates lipogenesis that previously was shown to be induced by T3 (39 ). We also saw induction of fatty acid transport protein mRNA, which encodes a plasma membrane protein that is highly expressed in liver that mediates the transport of long chain fatty acids into cells (40 ). We did not observe induction of malic enzyme mRNA, which is known to be stimulated by T3 (17 39 41 ). It is possible that malic enzyme may have a delayed response to T3 or may be regulated by Spot 14 (39 42 ). Recently, it has been reported that T3 also can down-regulate cytochrome p450 4A3 (Cyp4A3) mRNA (43 ) and that Cyp4A10 mRNA is increased in diabetic rats (44 ). We observed that T3 decreases mitochondrial acyltransferase Cyp4A10 mRNAs, which, in turn, could reduce fatty acid oxidation acutely and increase lipogenesis.

T3 also decreased another downstream insulin signaling component, PHAS (phosphorylated heat-and acid-stable protein), which is the 4E(eIF-4E)-binding protein that complexes with the eukaryotic initiation factor, eIF4E, and inhibits eIF-4E-dependent translation. Phosphorylation of PHAS by insulin signaling causes dissociation of PHAS from the PHAS-eIF-4E complex, and leads to increased translation (45 46 ). Since T3 down-regulated PHAS, it is possible that T3, a known hepatic mitogen, may have an insulin-mimetic effect with respect to protein synthesis. On the other hand, T3 decreases Akt2 mRNA expression and increases intracellular cAMP, which may decrease phosphorylation of PHAS (46 47 ) and thus inhibit translation. Despite studies of thyroid hormone regulation of protein synthesis (48 49 ), neither the detailed mechanism nor the net effects of T3 on translation are known.

Previous reports have shown that T3 has complex effects on hepatocyte proliferation and cell survival (50 51 52 ). Consistent with these effects, we observed changes in genes involved in apoptosis and cell cycle progression. In particular, genes involved in cell proliferation such as Bcl3, B61, and kinesin-like protein (Kip1p) were induced by T3. Bcl3 is an I{kappa}B-related protein that behaves differently than I{kappa}B as it can act as a coactivator for nuclear factor (NF){kappa}B homodimers (53 54 55 ). It also functions as a coactivator for AP-1 complexes and retinoid X receptors (56 ) and thus potentially may serve as a coactivator for TR itself. B61 is a glycosylphosphatidylinositol-linked protein, which serves as a ligand for Eck receptor protein-tyrosine kinase (57 ) and may act as a hepatic mitogen. Kip1p participates in the segregation of chromosomes during mitosis by modulating the movement of spindle assembly and chromosome distribution (58 ). Recent studies suggest that T3 stimulation of proliferation may be of clinical importance in gene therapy as it may promote the transfection of viral vectors into liver (59, 60).

Although T3 stimulates hepatocyte proliferation, it also can stimulate apoptosis in hepatocytes in which proliferation is pharmacologically blocked, and in amphibian tails during metamorphoses (52 61 ). In this connection, we found that several genes involved in apoptosis were regulated by T3, as T3 decreased expression of Akt2 and protein kinase C (PKC){theta} mRNA, and increased expression of the PKC inhibitor, (PKCi) mRNA. Akt2 can induce phosphorylation of caspase-9 to inhibit its protease activity, as well as activate NF{kappa}B (62 ). PKC{theta}, an atypical form of PKC, has been shown to be critically involved in important cell functions such as proliferation and cell survival. PKC{theta} activates I{kappa}B kinase B, which then can activate NF{kappa}B (63 ). Additionally, PKCi opposes the action of PKC, so induction of PKCi would promote apoptosis (64 ).

In our microarray studies, T3 negatively regulated several genes involved in glycoprotein synthesis such as ß-galactoside {alpha} 2,6-sialyltransferase, and {alpha}-2,3-sialyltransferase. Of note, hypothyroidism has been shown to induce {alpha}-2,3-sialyltransferase expression in pituitary thyrotrophs (65 ). The sialyltransferases catalyze the transfer of sialic acid from cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to terminal positions on sugar chains of glycoproteins and glycolipids (66 ) and are markers for many tumors (67 68 ). Finally, T3 negatively regulated genes involved in cellular immunity, cell matrix, cell structure, endocytosis, and mitochondrial function which, in turn, may represent novel areas of T3 action (Table 1Go).

To confirm and extend our findings on newly discovered target genes, we performed a separate time course experiment on T3 regulation of two newly identified target genes, Bcl-3 and {alpha} 2,3 sialyltransferase. mRNA was measured by Northern blot analyses from livers harvested from mice at various times after T3 treatment. Bcl-3 mRNA levels were induced approximately 10-fold 1 h after T3 treatment and declined to 5-fold by 3 h (Fig. 4AGo). {alpha}-2,3-Sialyltransferase mRNA levels decreased 1 h after T3 treatment and reached their nadir at 3 h. (Fig. 4BGo). It is possible that {alpha}-2,3 sialyltransferase and some of the other negatively regulated target genes identified by our microarray may serve as new markers of thyroid hormone action outside the pituitary, as well as tools for understanding the mechanism of negative regulation by nuclear hormone receptors.



View larger version (8K):
[in this window]
[in a new window]
  		Figure 4. Northern Blot Analysis of Bcl-3 and {alpha}-2,3-Sialyltransferase Expression in Hypothyroid and Hyperthyroid Mouse Liver

Liver biopsies were taken from PTU-treated mice at the indicated times (h) after thyroid hormone injection, and RNA was prepared as described in Materials and Methods. The y axis represents fold-induction or -repression of mRNA in T3-treated mice relative to basal levels mRNA levels in hypothyroid mice. The x axis shows time of sampling after T3 injection. Data are mean ± SD (n > 3) and were normalized against the 36B4 mRNA signals. A, Time course of T3 induction of Bcl-3 in mouse livers. B, Time course of T3 repression of {alpha}-2,3-sialyltransferase in mouse livers.

 
Although the majority of the cells within the liver are hepatocytes, it is possible that regulated genes from other cell types (e.g. endothelial cells, Kupfer cells, red blood cells) may also have been detected by the microarray. Furthermore, although we studied gene expression relatively soon after T3 administration (6 h), it is not known whether all the target genes identified are regulated directly by T3. It is possible that intracellular factors may be rapidly induced which, in turn, may regulate some of the target genes we have described. Also, since this study was performed in vivo, it is possible that hormones that are regulated by T3 may regulate some of the target genes. In particular, GH is induced by T3 in rodents and was found to coregulate a small subset of T3-induced target genes that were studied by Oppenheimer and associates (69 ) using two-dimensional protein gel electrophoresis (69 ). Microarray studies using hypophysectomized mice, GH receptor knockout mice, or GH antagonists may help clarify this issue. Despite these potential limitations, our study has demonstrated the utility of cDNA microarrays to identify novel target genes in vivo and extend the applicability of this powerful technology beyond conventional cell culture systems.

In conclusion, we have used cDNA microarray technology to analyze gene expression changes in mouse liver after administration of thyroid hormone. We identified 55 target genes, most of which have not been described previously. Surprisingly, many of these target genes were negatively regulated. Two recent reports have demonstrated the broad patterns of gene expression that can occur in human disease (15 16 ). Similarly, we have observed changes in the patterns of gene expression at the genomic level after hormone stimulation. Thus, our findings have enhanced our awareness of the large repertoire of genes and the multiple cell processes and signaling pathways regulated by thyroid hormone. It is likely that such complex regulation of gene expression occurs in other target tissues regulated by thyroid hormone and by other hormones. The use of microarray technology in living animals is a powerful tool to study gene regulation in a physiological system. It will be useful in identifying novel pathways for hormone action and tumorigenesis. It also should prove valuable for drug design as it will enable characterization of agonist and antagonist properties of drugs as well as side effects based upon gene expression patterns.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS AND DISCUSSION
 MATERIALS AND METHODS
The European Journal of...
 REFERENCES
 
Animals
Six-week-old mice were obtained from Charles River Laboratories, Inc. (Wilmington, MA) and maintained in the animal care facility at NIH according to NIH animal care guidelines. Hypothyroid mice were fed a low iodine (loI) diet supplemented with 0.15% PTU purchased from Harlan Teklad Co. (Madison, WI) for 4 weeks (17 ). After 4 weeks on this diet, hyperthyroid mice were injected ip with 100 mg L-T3 or T4 per 100 g mouse body weight in 200 µl PBS. Control mice were injected with the same volume of PBS alone. Six hours after thyroid hormone injection, mice were killed by cervical dislocation. Livers were isolated for total RNA isolation. TSH measurements (kindly performed by Dr. Samuel Refetoff, University of Chicago, Chicago, IL) indicated that mice treated with PTU according to this protocol were profoundly hypothyroid before T3 or T4 administration (TSH 64–110 ng/ml, n = 4; nl 0.02–0.95 ng/ml).

RNA Preparation and Labeling
Total RNA was isolated from mouse livers by RNeasy kit (QIAGEN, Chatsworth, CA) and further purified by TRIZOL reagent (Life Technologies, Inc., Gaithersburg, MD). Total RNA (100 µg) was converted to cDNA by using SuperScript II RNA reverse transcriptase (Life Technologies, Inc.) as previously described (10 ). RNA isolated from hypothyroid mice was used to prepare cDNA probes labeled with Cy3-deoxyuridine triphosphate (dUTP) dUTP (Amersham Pharmacia Biotech, Piscataway, NJ), and RNA isolated from hyperthyroid mice was used to prepare cDNA labeled with Cy5-dUTP (Amersham Pharmacia Biotech). Labeled cDNA was purified using MicroCon 30 (Amicon, Inc., Beverly, MA).

cDNA Microarray
The cDNA microarrays contained 2,225 elements derived from murine EST clones obtained from Research Genetics, Inc. (Huntsville, AL) as previously described (10 ). PCR products generated from these clones were printed onto glass slides as previously described (9 10 ).

Hybridization and Scanning
Labeled cDNA from the hypothyroid mouse and either T3- or T4- treated mice were hybridized to a 1.0-cm2 microarray under a 14 x 14 mm glass coverslip overnight at 60 C in a custom-built hybridization chamber, and fluorescence intensities were analyzed by a custom-designed laser confocal microscope as previously described (10 18 ). Image analysis was performed using DEARRAY software (10 ).

Northern Blotting
Total RNA was prepared from mouse liver using TRIZOL reagent (Life Technologies, Inc.) according to the manufacturer’s instructions. Total RNA (20 µg) was separated on 1% agarose-formaldehyde gel and then transferred to a nylon transfer membrane (Schleicher & Schuell, Inc., Keene, NH). The blots were probed with gel purified {alpha}-[32P] dCTP-labeled fragments and exposed to a Biomax film(Eastman Kodak Co., Rochester, NY) at -70 C. mRNA signals were quantified using ImageQuant software (Molecular Dynamics, Inc., Sunnyvale, CA), and normalized with corresponding thyroid hormone-insensitive 36B4 signals. Fold-inductions were determined from hyperthyroid mice signal values divided by hypothyroid mice signal values within the same experiment.


   The European Journal of Endocrinology Prize
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS AND DISCUSSION
 MATERIALS AND METHODS
 The European Journal of...
REFERENCES
 
The European Journal of Endocrinology Prize is awarded during the European Congress of Endocrinology to a candidate who has significantly contributed to the advancement of knowledge in the field of endocrinology through publication.

The prize consists of a certificate and Euro 7,250 plus travelling expenses and will be presented during the Vth European Congress of Endocrinology to be held in Turin, Italy from June 9–13, 2001. Nominations should be submitted to the Chief Editor of the European Journal of Endocrinology, Professor Paolo Beck-Peccoz, Istituto di Scienze Endocrine, Piano Terra, Padiglione Granelli, IRCCS, Via Francesco Sforza 35, 20122 Milan, Italy, by December 31, 2000. For more detailed information please check our website at: www.eje.org or contact our office at the following e-mail address: eie@nikotron.com.


   ACKNOWLEDGMENTS
 
The authors would like to thank Drs. Leonard Kohn, Joseph Rall, Marc Reitman, Simeon Taylor (NIDDK), and Drs. Samuel Refetoff and Roy Weiss (University of Chicago) for helpful discussions.


   FOOTNOTES
 
Address requests for reprints to: Paul M. Yen, M.D. Molecular Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, NIDDK, NIH, Bethesda, Maryland 20892.

Received for publication January 11, 2000. Revision received February 21, 2000. Accepted for publication February 24, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS AND DISCUSSION
 MATERIALS AND METHODS
 The European Journal of...
 REFERENCES
 

  1. Oppenheimer JA, Schwartz HL, Mariash CN, Kinlaw WB, Wong NCW, Freake HC 1987 Advances in our understanding of thyroid hormone action at the cellular level. Endocr Rev 8:288–308[Abstract/Free Full Text]
  2. Lazar MA 1993 Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 14:348–399[Abstract/Free Full Text]
  3. Yen PM, Chin WW 1994 New advances in understanding the molecular mechanisms of thyroid hormone action. Trends Endocrinol Metab 5:65–72
  4. Williams GR, Brent GA 1995 Thyroid hormone response elements. In: Weintraub B (ed) Molecular Endocrinology: Basic Concepts, Clinical Correlations. Raven Press, New York, 1995, pp 217–239
  5. Schena M, Shalon D, Davis RW, Brown PO 1995 Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–70[Abstract/Free Full Text]
  6. Schena M, Shalon D, Heller R, Chai A, Brown PO, Davis RW 1996 Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci USA 93:10614–10619[Abstract/Free Full Text]
  7. Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JCF, Trent JM, Staudt LM, Hudson Jr J, Boguski MS, Lashkari D, Shalon D, Botstein D, Brown PO 1999 The transcriptional program in the response of human fibroblasts to serum. Science 283:83–87[Abstract/Free Full Text]
  8. Wang K, Gan L, Jeffery E, Gayle M, Gown AM, Skelly M, Nelson PS, Ng WV, Schummer M, Hood L, Mulligan J 1999 Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray. Gene 229:101–108[CrossRef][Medline]
  9. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM 1996 Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 14:457–460[CrossRef][Medline]
  10. Khan J, Bittner ML, Saal LH, Teichmann U, Azorsa DO, Gooden GC, Pavan WJ, Trent JM, Meltzer PS 1999 cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci USA 96:13264–13269[Abstract/Free Full Text]
  11. Lee CK, Klopp RG, Weindruch R, Prolla TA 1999 Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390–1393[Abstract/Free Full Text]
  12. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B 1998 Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9:3273–3297[Abstract/Free Full Text]
  13. Bryant Z, Subrahmanyan L, Tworoger M, LaTray L, Liu CR, Li MJ, van den Engh G, Ruohola-Baker H 1999 Characterization of differentially expressed genes in purified Drosophila follicle cells: toward a general strategy for cell type- specific developmental analysis. Proc Natl Acad Sci USA 96:5559–5564[Abstract/Free Full Text]
  14. Marton MJ, DeRisi JL, Bennett HA, Iyer VR, Meyer MR, Roberts CJ, Stoughton R, Burchard J, Slade D, Dai H, Bassett Jr DE, Hartwell LH, Brown PO, Friend SH 1998 Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat Med 4:1293–1301[CrossRef][Medline]
  15. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES 1999 Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–537[Abstract/Free Full Text]
  16. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM 2000 Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511[CrossRef][Medline]
  17. Weiss RE, Murata Y, Cua K, Hayashi Y, Seo H, Refetoff S 1998 Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor ß-deficient mice. Endocrinology 139:4945–4952[Abstract/Free Full Text]
  18. Khan J, Saal LH, Bittner ML, Chen Y, Trent JM, Meltzer PS 1999 Expression profiling in cancer using cDNA microarrays. Electrophoresis 20:223–229[CrossRef][Medline]
  19. Brent GA 1994 The molecular basis of thyroid hormone action. N Engl J Med 331:847–853[Free Full Text]
  20. Zhang, L, Zhou W, Velculescu VE, Kern SE, Hruban RH, Hamilton SR, Vogelstein B, Kinzler KW 1997 Gene expression profiles in normal and cancer cells. Science 276:1268–1272[Abstract/Free Full Text]
  21. Arrondo JL, Artetxe J, Sancho MJ, Macarulla JM 1981 Liver glycogen metabolism in chicken. Activation prior to triiodothyronine-induced protein synthesis enhancement. Horm Metab Res 13:92–4[Medline]
  22. Muller MJ, Thomsen A, Sibrowski W, Seitz HJ 1982 3,5,3'-Triiodothyronine-induced synthesis of rat liver phosphoenolpyruvate carboxykinase. Endocrinology 111:1469–1475[Abstract/Free Full Text]
  23. Bratusch-Marrain PR, Komjati M, Waldhausl WK 1985 Glucose metabolism in noninsulin-dependent diabetic patients with experimental hyperthyroidism. J Clin Endocrinol Metab 60:1063–1068[Abstract/Free Full Text]
  24. Karlander SG, Khan A, Wajngot A, Torring O, Vranic M, Efendic S 1989 Glucose turnover in hyperthyroid patients with normal glucose tolerance. J Clin Endocrinol Metab 68:780–786[Abstract/Free Full Text]
  25. Folli F, Saad MJ, Backer JM, Kahn CR 1993 Regulation of phosphatidylinositol 3-kinase activity in liver and muscle of animal models of insulin-resistant and insulin- deficient diabetes mellitus. J Clin Invest 92:1787–1794
  26. Egawa K, Sharma PM, Nakashima N, Huang Y, Huver E, Boss GR, Olefsky JM 1999 Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. J Biol Chem 274:14306–14314[Abstract/Free Full Text]
  27. Hill MM, Clark SF, Tucker DF, Birnbaum MJ, James DE, Macaulay SL 1999 A role for protein kinase Bbeta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes. Mol Cell Biol 19:7771–7781[Abstract/Free Full Text]
  28. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA 1995 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785–789[CrossRef][Medline]
  29. Mitsuuchi Y, Johnson SW, Moonblatt S, Testa JR 1998 Translocation and activation of AKT2 in response to stimulation by insulin. J Cell Biochem 70:433–41[CrossRef][Medline]
  30. Carpentier JL, Paccaud JP, Gorden P, Rutter WJ, Orci L 1992 Insulin-induced surface redistribution regulates internalization of the insulin receptor and requires its autophosphorylation. Proc Natl Acad Sci USA 89:162–166[Abstract/Free Full Text]
  31. Choice CV, Howard MJ, Poy MN, Hankin MH, Najjar SM 1998 Insulin stimulates pp120 endocytosis in cells co-expressing insulin receptors. J Biol Chem 273:22194–22200[Abstract/Free Full Text]
  32. Krischer J, Gilbert A, Gorden P, Carpentier JL 1993 Endocytosis is inhibited in hepatocytes from diabetic rats. Diabetes 42:1303–1309[Abstract]
  33. Angervo M, Leinonen P, Koistinen R, Julkunen M, Seppala M 1993 Tri-iodothyronine and cycloheximide enhance insulin-like growth factor-binding protein-1 gene expression in human hepatoma cells. J Mol Endocrinol 10:7–13[Abstract/Free Full Text]
  34. Nebioglu S, Wathanaronchai P, Nebioglu D, Pruden EL, Gibson DM 1990 Mechanisms underlying enhanced glycogenolysis in livers of 3,5,3'-triiodothyronine-treated rats. Am J Physiol 258: E109–E116
  35. Muller MJ, Seitz HJ 1983 Interaction of thyroid hormones and cyclic AMP in the stimulation of hepatic gluconeogenesis. Biochim Biophys Acta 756:360–368[Medline]
  36. Shaheen O, Morgan DW, Wilcox HG, Keyes WG, Heimberg M 1982 Modulation by thyroid status of the actions of glucagon and dibutyryl adenosine 3',5'-monophosphate on metabolism of free fatty acids by the isolated perfused rat liver. Endocrinology 110:1740–1748[Abstract/Free Full Text]
  37. Bahouth SW 1995 Thyroid hormone regulation of transmembrane signalling in neonatal rat ventricular myocytes by selective alteration of the expression and coupling of G-protein {alpha}-subunits. Biochem J 307:831–841
  38. Morgan DW, Shaheen O, Keyes WG, Heimberg M 1982 Modulation by thyroid status of hepatic low Km phosphodiesterase. Endocrinology 110:260–264[Abstract/Free Full Text]
  39. Cunningham BA, Moncur JT, Huntington JT, Kinlaw WB 1998 "Spot 14" protein: a metabolic integrator in normal and neoplastic cells. Thyroid 8:815–825[Medline]
  40. Hirsch D, Stahl A, Lodish HF 1998 A family of fatty acid transporters conserved from mycobacterium to man. Proc Natl Acad Sci USA 95:8625–8629[Abstract/Free Full Text]
  41. Blennemann B, Leahy P, Kim T, Freake H 1995 Tissue-specific regulation of lipogenic mRNAs by thyroid hormone. Mol Cell Endocrinol 110:1–8[CrossRef][Medline]
  42. Brown SB, Maloney M, Kinlaw WB 1997 "Spot 14" protein functions at the pretranslational level in the regulation of hepatic metabolism by thyroid hormone and glucose. J Biol Chem 272:2163–6[Abstract/Free Full Text]
  43. Webb SJ, Xiao GH, Geoghegan TE, Prough RA 1996 Regulation of CYP4A expression in rat by dehydroepiandrosterone and thyroid hormone. Mol Pharmacol 49:276–287[Abstract]
  44. Enriquez A, Leclercq I, Farrell GC, Robertson G 1999 Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats. Biochem Biophys Res Commun 255:300–306[CrossRef][Medline]
  45. Kohn AD, Barthel A, Kovacina KS, Boge A, Wallach B, Summers SA, Birnbaum MJ, Scott PH, Lawrence Jr JC, Roth RA 1998 Construction and characterization of a conditionally active version of the serine/threonine kinase Akt. J Biol Chem 273:11937–11943[Abstract/Free Full Text]
  46. Takata M, Ogawa W, Kitamura T, Hino Y, Kuroda S, Kotani K, Klip A, Gingras AC, Sonenberg N, Kasuga M 1999 Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1). J Biol Chem 274:20611–20618[Abstract/Free Full Text]
  47. Scott PH, Lawrence Jr JC 1998 Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3–L1 adipocytes. J Biol Chem 273:34496–34501[Abstract/Free Full Text]
  48. Carter WJ, Faas FH, Wynn J 1975 Demonstration of thyroxine-stimulated incorporation of amino acid into peptide linkage in mitochondria-free system. J Biol Chem 250:3588–3594[Abstract/Free Full Text]
  49. Mathews RW, Oronsky A, Haschemeyer AE 1973 Effect of thyroid hormone on polypeptide chain assembly kinetics in liver protein synthesis in vivo. J Biol Chem 248:1329–33[Abstract/Free Full Text]
  50. Ohmura T, Katyal SL, Locker J, Ledda-Columbano GM, Columbano A, Shinozuka H 1997 Induction of cellular DNA synthesis in the pancreas and kidneys of rats by peroxisome proliferators, 9-cis retinoic acid, and 3,3',5-triiodo-L-thyronine. Cancer Res 57:795–798[Abstract/Free Full Text]
  51. Torres S, Diaz BP, Cabrera JJ, Diaz-Chico JC, Diaz-Chico BN, Lopez-Guerra A 1999 Thyroid hormone regulation of rat hepatocyte proliferation and polyploidization. Am J Physiol 276: G155–163
  52. Oren R, Dabeva MD, Karnezis AN, Petkov PM, Rosencrantz R, Sandhu JP, Moss SF, Wang S, Hurston E, Laconi E, Holt PR, Thung SN, Zhu L, Shafritz DA 1999 Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes. Hepatology 30:903–913[CrossRef][Medline]
  53. Bundy DL, McKeithan TW 1997 Diverse effects of BCL3 phosphorylation on its modulation of NF-{kappa}B p52 homodimer binding to DNA. J Biol Chem 272:33132–33139[Abstract/Free Full Text]
  54. Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U 1993 The oncoprotein Bcl-3 directly transactivates through {kappa} B motifs via association with DNA-binding p50B homodimers. Cell 72:729–739[CrossRef][Medline]
  55. Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A 1999 The Bcl-3 oncoprotein acts as a bridging factor between NF-{kappa}B/Rel and nuclear co-regulators. Oncogene 18:3316–3323[CrossRef][Medline]
  56. Na SY, Choi HS, Kim JW, Na DS, Lee JW 1998 Bcl3, an I{kappa}B protein, as a novel transcription coactivator of the retinoid X receptor. J Biol Chem 273:30933–30938[Abstract/Free Full Text]
  57. Shao H, Pandey A, O’Shea KS, Seldin M, Dixit VM 1995 Characterization of B61, the ligand for the Eck receptor protein- tyrosine kinase. J Biol Chem 270:5636–5641[Abstract/Free Full Text]
  58. Saunders WS, Hoyt MA 1992 Kinesin-related proteins required for structural integrity of the mitotic spindle. Cell 70:451–458[CrossRef][Medline]
  59. Francavilla A, Carr BI, Azzarone A, Polimeno L, Wang Z, Van Thiel DH, Subbotin V, Prelich JG, Starzl TE 1994 Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro. Hepatology 20:1237–1241[CrossRef][Medline]
  60. Forbes SJ, Themis M, Alison MR, Selden C, Coutelle C, Hodgson HJ 1998 Retroviral gene transfer to the liver in vivo during tri-iodothyronine induced hyperplasia. Gene Ther 5:552–555[CrossRef][Medline]
  61. Su Y, Damjanovski S, Shi Y, Shi YB 1999 Molecular and cellular basis of tissue remodeling during amphibian metamorphosis. Histol Histopathol 14:175–183[Medline]
  62. Romashkova JA, Makarov SS 1999 NF-{kappa}B is a target of AKT in anti-apoptotic PDGF signalling. Nature 401:86–90[CrossRef][Medline]
  63. Lallena MJ, Diaz-Meco MT, Bren G, Paya CV, Moscat J 1999 Activation of I{kappa}B kinase ß by protein kinase C isoforms. Mol Cell Biol 19:2180–2188[Abstract/Free Full Text]
  64. Pearson JD, DeWald DB, Mathews WR, Mozier NM, Zurcher-Neely HA, Heinrikson RL, Morris MA, McCubbin WD, McDonald JR, Fraser ED, Vogel HJ, Kay CM, Walsh MP 1990 Amino acid sequence and characterization of a protein inhibitor of protein kinase C. J Biol Chem 265:4583–4591[Abstract/Free Full Text]
  65. Helton TE, Magner JA 1995 ß-Galactoside {alpha}-2,3-sialyltransferase messenger RNA increases in thyrotrophs of hypothyroid mice. Thyroid 5:315–317[Medline]
  66. Okajima T, Fukumoto S, Miyazaki H, Ishida H, Kiso M, Furukawa K, Urano T 1999 Molecular cloning of a novel {alpha}2,3-sialyltransferase (ST3Gal VI) that sialylates type II lactosamine structures on glycoproteins and glycolipids. J Biol Chem 274:11479–11486[Abstract/Free Full Text]
  67. Liu CK, Schmied R, Waxman S 1979 The specific release of sialytransferase activity by human hepatoma cell lines. Clin Chim Acta 98:225–233[CrossRef][Medline]
  68. Alhadeff JA, Holzinger RT 1982 Sialyltransferase, sialic acid and sialoglycoconjugates in metastatic tumor and human liver tissue. Int J Biochem 14:119–126[CrossRef][Medline]
  69. Seelig S, Liaw C, Towle HC, Oppenheimer JH 1981 Thyroid hormone attenuates and augments hepatic gene expression at a pretranslational level. Proc Natl Acad Sci USA 78:4733–7[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
I. H. Chan and M. L. Privalsky
Isoform-Specific Transcriptional Activity of Overlapping Target Genes that Respond to Thyroid Hormone Receptors {alpha}1 and {beta}1
Mol. Endocrinol., November 1, 2009; 23(11): 1758 - 1775.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
W. E. Visser, K. A. Heemstra, S. M. A. Swagemakers, Z. Ozgur, E. P. Corssmit, J. Burggraaf, W. F. J. van Ijcken, P. J. van der Spek, J. W. A. Smit, and T. J. Visser
Physiological Thyroid Hormone Levels Regulate Numerous Skeletal Muscle Transcripts
J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3487 - 3496.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. Astapova, L. J. Lee, C. Morales, S. Tauber, M. Bilban, and A. N. Hollenberg
The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo
PNAS, December 9, 2008; 105(49): 19544 - 19549.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. de Lange, R. Senese, F. Cioffi, M. Moreno, A. Lombardi, E. Silvestri, F. Goglia, and A. Lanni
Rapid Activation by 3,5,3'-L-Triiodothyronine of Adenosine 5'-Monophosphate-Activated Protein Kinase/Acetyl-Coenzyme A Carboxylase and Akt/Protein Kinase B Signaling Pathways: Relation to Changes in Fuel Metabolism and Myosin Heavy-Chain Protein Content in Rat Gastrocnemius Muscle in Vivo
Endocrinology, December 1, 2008; 149(12): 6462 - 6470.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. Crump, S. Chiu, C. Egloff, and S. W. Kennedy
Effects of Hexabromocyclododecane and Polybrominated Diphenyl Ethers on mRNA Expression in Chicken (Gallus domesticus) Hepatocytes
Toxicol. Sci., December 1, 2008; 106(2): 479 - 487.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
A. Wulf, M. G Wetzel, M. Kebenko, M. Kroger, A. Harneit, J. Merz, and J. M Weitzel
The role of thyroid hormone receptor DNA binding in negative thyroid hormone-mediated gene transcription
J. Mol. Endocrinol., July 1, 2008; 41(1): 25 - 34.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
E. Silvestri, A. Lombardi, P. de Lange, L. Schiavo, A. Lanni, F. Goglia, T. J. Visser, and M. Moreno
Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels
Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1160 - E1168.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Dong, C. L. Yauk, A. Williams, A. Lee, G. R. Douglas, and M. G. Wade
Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element
Endocrinology, August 1, 2007; 148(8): 3932 - 3940.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
G. Calamita, M. Moreno, D. Ferri, E. Silvestri, P. Roberti, L. Schiavo, P. Gena, M. Svelto, and F. Goglia
Triiodothyronine modulates the expression of aquaporin-8 in rat liver mitochondria
J. Endocrinol., January 1, 2007; 192(1): 111 - 120.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
O A Sukocheva and D O Carpenter
Anti-apoptotic effects of 3,5,3'-tri-iodothyronine in mouse hepatocytes.
J. Endocrinol., November 1, 2006; 191(2): 447 - 458.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
P. A. Dawson, B. Gardiner, S. Grimmond, and D. Markovich
Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice
Physiol Genomics, September 14, 2006; 26(2): 116 - 124.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
M. Nygard, N. Becker, B. Demeneix, K. Pettersson, and M. Bondesson
Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.
J. Mol. Endocrinol., June 1, 2006; 36(3): 517 - 530.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. H. Conrad, Y. Zhang, A. R. Walker, L. A. Olberding, A. Hanzlick, A. J. Zimmer, R. Morffi, and G. W. Conrad
Thyroxine Affects Expression of KSPG-Related Genes, the Carbonic Anhydrase II Gene, and KS Sulfation in the Embryonic Chicken Cornea
Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 120 - 132.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. H. D. Bassett, R. Swinhoe, O. Chassande, J. Samarut, and G. R. Williams
Thyroid Hormone Regulates Heparan Sulfate Proteoglycan Expression in the Growth Plate
Endocrinology, January 1, 2006; 147(1): 295 - 305.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Frenzel, K. Krohn, M. Eszlinger, A. Tonjes, and R. Paschke
Sialylation of Human Thyrotropin Receptor Improves and Prolongs Its Cell-Surface Expression
Mol. Pharmacol., October 1, 2005; 68(4): 1106 - 1113.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
W. Wan, B. Farboud, and M. L. Privalsky
Pituitary Resistance to Thyroid Hormone Syndrome Is Associated with T3 Receptor Mutants that Selectively Impair {beta}2 Isoform Function
Mol. Endocrinol., June 1, 2005; 19(6): 1529 - 1542.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Meng, P. Webb, Y.-F. Yang, M. Shuen, A. F. Yousef, J. D. Baxter, J. S. Mymryk, and P. G. Walfish
E1A and a nuclear receptor corepressor splice variant (N-CoRI) are thyroid hormone receptor coactivators that bind in the corepressor mode
PNAS, May 3, 2005; 102(18): 6267 - 6272.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. M. Zavacki, H. Ying, M. A. Christoffolete, G. Aerts, E. So, J. W. Harney, S.-y. Cheng, P. R. Larsen, and A. C. Bianco
Type 1 Iodothyronine Deiodinase Is a Sensitive Marker of Peripheral Thyroid Status in the Mouse
Endocrinology, March 1, 2005; 146(3): 1568 - 1575.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. M. Yen
Studying Hormonal Regulation by Microarrays: Distinguishing the Trees from the Forest
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1241 - 1242.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. C. Moeller, A. M. Dumitrescu, R. L. Walker, P. S. Meltzer, and S. Refetoff
Thyroid Hormone Responsive Genes in Cultured Human Fibroblasts
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 936 - 943.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H.-G. Yoon, Y. Choi, P. A. Cole, and J. Wong
Reading and Function of a Histone Code Involved in Targeting Corepressor Complexes for Repression
Mol. Cell. Biol., January 1, 2005; 25(1): 324 - 335.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
K. T. Morgan, Z. Jayyosi, M. A. Hower, M. V. Pino, T. M. Connolly, K. Kotlenga, J. Lin, M. Wang, H.-L. Schmidts, M. S. Bonnefoi, et al.
The Hepatic Transcriptome as a Window on Whole-Body Physiology and Pathophysiology
Toxicol Pathol, January 1, 2005; 33(1): 136 - 145.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. J. Mengeling, F. Pan, and M. L. Privalsky
Novel Mode of Deoxyribonucleic Acid Recognition by Thyroid Hormone Receptors: Thyroid Hormone Receptor {beta}-Isoforms Can Bind as Trimers to Natural Response Elements Comprised of Reiterated Half-Sites
Mol. Endocrinol., January 1, 2005; 19(1): 35 - 51.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. L. R. Williams, J. Simpson, C. Delahunty, S. A. Ogston, J. J. Bongers-Schokking, N. Murphy, H. van Toor, S.-Y. Wu, T. J. Visser, R. Hume, et al.
Developmental Trends in Cord and Postpartum Serum Thyroid Hormones in Preterm Infants
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5314 - 5320.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. Adamson, N. Maitra, J. Bahl, K. Greer, S. Klewer, J. Hoying, and E. Morkin
Regulation of Gene Expression in Cardiomyocytes by Thyroid Hormone and Thyroid Hormone Analogs 3,5-Diiodothyropropionic Acid and CGS 23425 [N-[3,5-Dimethyl-4-(4'-hydroxy-3'-isopropylphenoxy)-phenyl]-oxamic Acid]
J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 164 - 171.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. M. R. Moore, S. J. Galicia, A. C. McReynolds, N.-H. Nguyen, T. S. Scanlan, and R. K. Guy
Quantitative Proteomics of the Thyroid Hormone Receptor-Coregulator Interactions
J. Biol. Chem., June 25, 2004; 279(26): 27584 - 27590.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C.-h. Shih, S.-L. Chen, C.-C. Yen, Y.-H. Huang, C.-d. Chen, Y.-S. Lee, and K.-h. Lin
Thyroid Hormone Receptor-Dependent Transcriptional Regulation of Fibrinogen and Coagulation Proteins
Endocrinology, June 1, 2004; 145(6): 2804 - 2814.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Otsuki, H. Gao, K. Dahlman-Wright, C. Ohlsson, N. Eguchi, Y. Urade, and J.-A. Gustafsson
Specific Regulation of Lipocalin-Type Prostaglandin D Synthase in Mouse Heart by Estrogen Receptor {beta}
Mol. Endocrinol., September 1, 2003; 17(9): 1844 - 1855.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. C. Helbing, K. Werry, D. Crump, D. Domanski, N. Veldhoen, and C. M. Bailey
Expression Profiles of Novel Thyroid Hormone-Responsive Genes and Proteins in the Tail of Xenopus laevis Tadpoles Undergoing Precocious Metamorphosis
Mol. Endocrinol., July 1, 2003; 17(7): 1395 - 1409.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Fourcade, S. Savary, C. Gondcaille, J. Berger, A. Netik, F. Cadepond, M. El Etr, B. Molzer, and M. Bugaut
Thyroid Hormone Induction of the Adrenoleukodystrophy-Related Gene (ABCD2)
Mol. Pharmacol., June 1, 2003; 63(6): 1296 - 1303.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
A. J Forhead, K. R Poore, J. Mapstone, and A. L Fowden
Developmental regulation of hepatic and renal gluconeogenic enzymes by thyroid hormones in fetal sheep during late gestation
J. Physiol., May 1, 2003; 548(3): 941 - 947.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Mukhopadhyay, M. Plateroti, S. Anant, F. Nassir, J. Samarut, and N. O. Davidson
Thyroid Hormone Regulates Hepatic Triglyceride Mobilization and Apolipoprotein B Messenger Ribonucleic Acid Editing in a Murine Model of Congenital Hypothyroidism
Endocrinology, February 1, 2003; 144(2): 711 - 719.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Nygard, G. M. Wahlstrom, M. V. Gustafsson, Y. M. Tokumoto, and M. Bondesson
Hormone-Dependent Repression of the E2F-1 Gene by Thyroid Hormone Receptors
Mol. Endocrinol., January 1, 2003; 17(1): 79 - 92.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. M. Sadow, O. Chassande, K. Gauthier, J. Samarut, J. Xu, B. W. O'Malley, and R. E. Weiss
Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action
Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E36 - E46.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Flores-Morales, H. Gullberg, L. Fernandez, N. Stahlberg, N. H. Lee, B. Vennstrom, and G. Norstedt
Patterns of Liver Gene Expression Governed by TR{beta}
Mol. Endocrinol., June 1, 2002; 16(6): 1257 - 1268.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Soulet and S. Rivest
Perspective: How to Make Microarray, Serial Analysis of Gene Expression, and Proteomic Relevant to Day-to-Day Endocrine Problems and Physiological Systems
Endocrinology, June 1, 2002; 143(6): 1995 - 2001.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. A. Mong, C. Krebs, and D. W. Pfaff
Perspective: Micoarrays and Differential Display PCR--Tools for Studying Transcript Levels of Genes in Neuroendocrine Systems
Endocrinology, June 1, 2002; 143(6): 2002 - 2006.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Spada and P. Beck-Peccoz
Editorial: New Strategy to Solve the Etiopathogenetic Conundrum of Pituitary Adenomas
Endocrinology, February 1, 2002; 143(2): 343 - 346.
[Full Text] [PDF]

Home page
 Genome ResHome page
K. Clement, N. Viguerie, M. Diehn, A. Alizadeh, P. Barbe, C. Thalamas, J. D. Storey, P. O. Brown, G. S. Barsh, and D. Langin
In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone
Genome Res., February 1, 2002; 12(2): 281 - 291.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
F. Flamant, A.-L. Poguet, M. Plateroti, O. Chassande, K. Gauthier, N. Streichenberger, A. Mansouri, and J. Samarut
Congenital Hypothyroid Pax8-/- Mutant Mice Can Be Rescued by Inactivating the TR{alpha} Gene
Mol. Endocrinol., January 1, 2002; 16(1): 24 - 32.
[Abstract] [Full Text] [PDF]

Home page
 CROBMHome page
K. Iida and I. Nishimura
GENE EXPRESSION PROFILING BY DNA MICROARRAY TECHNOLOGY
Critical Reviews in Oral Biology & Medicine, January 1, 2002; 13(1): 35 - 50.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. M. Weitzel, C. Radtke, and H. J. Seitz
Two thyroid hormone-mediated gene expression patterns in vivo identified by cDNA expression arrays in rat
Nucleic Acids Res., December 15, 2001; 29(24): 5148 - 5155.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Mansen, F. Yu, D. Forrest, L. Larsson, and B. Vennstrom
TRs Have Common and Isoform-Specific Functions in Regulation of the Cardiac Myosin Heavy Chain Genes
Mol. Endocrinol., December 1, 2001; 15(12): 2106 - 2114.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A. J. Kreeft, C. J.A. Moen, M. H. Hofker, R. R. Frants, E. Vreugdenhil, M. J.J. Gijbels, L. M. Havekes, and N. A. Datson
Identification of Differentially Regulated Genes in Mildly Hyperlipidemic ApoE3-Leiden Mice by Use of Serial Analysis of Gene Expression
Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1984 - 1990.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. C. Pritchard, L. Hsu, J. Delrow, and P. S. Nelson
Project normal: Defining normal variance in mouse gene expression
PNAS, November 6, 2001; 98(23): 13266 - 13271.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. Dupont, J. Khan, B.-H. Qu, P. Metzler, L. Helman, and D. LeRoith
Insulin and IGF-1 Induce Different Patterns of Gene Expression in Mouse Fibroblast NIH-3T3 Cells: Identification by cDNA Microarray Analysis
Endocrinology, November 1, 2001; 142(11): 4969 - 4975.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. D. Miller, K. S. Park, Q. M. Guo, N. W. Alkharouf, R. L. Malek, N. H. Lee, E. T. Liu, and S.-y. Cheng
Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-Stimulated Cell Proliferation
Mol. Cell. Biol., October 1, 2001; 21(19): 6626 - 6639.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Akutsu, R. Lin, Y. Bastien, A. Bestawros, D. J. Enepekides, M. J. Black, and J. H. White
Regulation of Gene Expression by 1{{alpha}},25-Dihydroxyvitamin D3 and Its Analog EB1089 under Growth-Inhibitory Conditions in Squamous Carcinoma Cells
Mol. Endocrinol., July 1, 2001; 15(7): 1127 - 1139.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
P. M. Yen
Physiological and Molecular Basis of Thyroid Hormone Action
Physiol Rev, July 1, 2001; 81(3): 1097 - 1142.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. Sudbrak, G. Wieczorek, U. A. Nuber, W. Mann, R. Kirchner, F. Erdogan, C. J. Brown, D. Wohrle, P. Sterk, V. M. Kalscheuer, et al.
X chromosome-specific cDNA arrays: identification of genes that escape from X-inactivation and other applications
Hum. Mol. Genet., January 1, 2001; 10(1): 77 - 83.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. Sharma and J. D. Fondell
Temporal Formation of Distinct Thyroid Hormone Receptor Coactivator Complexes in HeLa Cells
Mol. Endocrinol., December 1, 2000; 14(12): 2001 - 2009.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
Y. Wu, B. Xu, and R. J. Koenig
Thyroid Hormone Response Element Sequence and the Recruitment of Retinoid X Receptors for Thyroid Hormone Responsiveness
J. Biol. Chem., February 2, 2001; 276(6): 3929 - 3936.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Feng, Y. Jiang, P. Meltzer, and P. M. Yen
Transgenic Targeting of a Dominant Negative Corepressor to Liver Blocks Basal Repression by Thyroid Hormone Receptor and Increases Cell Proliferation
J. Biol. Chem., April 27, 2001; 276(18): 15066 - 15072.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Feng, X.
Right arrow Articles by Yen, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feng, X.
Right arrow Articles by Yen, P. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals