Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The technique of reverse transcriptase-polymerase chain reaction differential display was used to identify thyroid hormone (TH) responsive mRNAs in the adult rat cerebral tissue. A partial cDNA (0.76 kb) was cloned and sequenced. Comparison of the sequence to the GenBank data base showed almost 100% homology to mouse translational repressor (NAT-1) mRNA 3'-end. In a northern blot analysis this cDNA hybridized with a mRNA whose expression in hyperthyroid rat cerebral tissue was approximately 6-fold higher than in euthyroid rats. The time course studies showed a rapid induction of this mRNA within 3 h following thyroxine administration. This mRNA is widely expressed in various tissues, and in hepatic tissue it is also TH responsive. To determine if TH responsiveness of this mRNA persists during aging, 25-month-old aged rats were studied and the results were compared with those of 4-month-old rats. Unlike young mature rats, the TH responsiveness of NAT-1 mRNA in both the cerebral and hepatic tissue of aged rats was blunted. It is concluded that cerebral tissue in aging rats beyond the developmental stages, like the hepatic tissue, is associated with altered TH responsiveness.
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PMID:Novel translational repressor (NAT-1) expression is modified by thyroid state and age in brain and liver. 991 72

Using a mouse Leydig tumor cell line, we explored the mechanisms involved in thyroid hormone-induced steroidogenic acute regulatory (StAR) protein gene expression, and steroidogenesis. Triiodothyronine (T3) induced a approximately 3.6-fold increase in the steady-state level of StAR mRNA which paralleled with those of the acute steroid response ( approximately 4.0-fold), as monitored by quantitative reverse transcriptase-polymerase chain reaction assay and progesterone production, respectively. The T3-stimulated progesterone production was effectively inhibited by actinomycin-D or cycloheximide, indicating the requirement of on-going mRNA and protein synthesis. T3 displayed the highest affinity of [125I]iodo-T3 binding and was most potent in stimulating StAR mRNA expression. In accordance, T3 significantly increased testosterone production in primary cultures of adult mouse Leydig cells. The T3 and human chorionic gonadotropin (hCG) effects on StAR expression were similar in magnitude and additive. Cells expressing steroidogenic factor 1 (SF-1) showed marginal elevation of StAR expression, but coordinately increased T3-induced StAR mRNA expression and progesterone levels. In contrast, overexpression of DAX-1 markedly diminished the SF-1 mRNA expression, and concomitantly abolished T3-mediated responses. Noteworthy, T3 augmented the SF-1 mRNA expression while inhibition of the latter by DAX-1 strongly impaired T3 action. Northern hybridization analysis revealed four StAR transcripts which increased 3-6-fold following T3 stimulation. These observations clearly identified a regulatory cascade of thyroid hormone-stimulated StAR expression and steroidogenesis that provides novel insight into the importance of a thyroid-gonadal connection in the hormonal control of Leydig cell steroidogenesis.
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PMID:Molecular mechanisms of thyroid hormone-stimulated steroidogenesis in mouse leydig tumor cells. Involvement of the steroidogenic acute regulatory (StAR) protein. 1002 15

The thyroid stimulating hormone (TSH)-immunoreactive cells (TSH cells) in the pars tuberalis (PT-TSH cell) of the male rat pituitary gland show an intense spot-like TSH immunoreaction in the paranuclear cytoplasm. However, the ontogenic origin and characteristics of these spot-like stained PT-TSH cells remain to be elucidated. The present study was designed to investigate the distribution and characteristics of PT-TSH cells in the foetal and adult rat pituitary by immunostaining for Pit-1 factor and thyroid hormone receptors (TRs) and reverse transcriptase-polymerase chain reaction (RT-PCR). TSH cells first appeared in the PT at 15.5 days of gestation and were either stained diffusely throughout the cytoplasm or displayed a strongly stained, spotty appearance in the paranuclear region. By 15.5 days of gestation, the rostral part of the PT consisted of columnar epithelium, in which TSH immunoreactivity was spot-like in the apical region of cytoplasm corresponding to the Golgi apparatus. At the 16.5 days of gestation, TSH cells were present in the pars distalis (PD); however, the cells were mostly larger and polygonal with strong staining throughout the cytoplasm. These differences between the PT and PD were retained throughout foetal and neonatal rat development. The TSH cells in the PD of the adult or gestational rat were observed to contain Pit-1 factor by double immunostaining. However, TSH cells in the PT lacked Pit-1 factor. RT-PCR confirmed the absence of Pit-1 and TRbeta2 mRNA in the PT of the adult and late gestation rat pituitary gland. These results suggest that apparently distinct types of TSH cells in the PT develop independently from TSH cells in the PD.
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PMID:Characterization of TSH-positive cells in foetal rat pars tuberalis that fail to express Pit-1 factor and thyroid hormone beta2 receptors. 1020 14

Amiodarone, a powerful antiarrhythmic drug, may exert its effect by antagonism of the thyroid hormone, probably at the receptor level. The aim of this study was to investigate whether amiodarone affects the levels of thyroid hormone receptor (TR) messenger RNA (mRNA) subtypes in mouse hearts. Mice were treated with 10, 25, and 50 mg/kg body weight (BW) amiodarone or vehicle (propyleneglycol) intraperitoneally, daily for 14 days. The heart rate dose-dependently decreased in the 25 mg/kg BW (p < 0.05) and 50 mg/kg BW (p < 0.005) amiodarone-treated mice compared with control. Serum T3 levels were significantly decreased by 25% (4.2 +/- 0.7 pM) in the 50 mg/kg BW amiodarone group in comparison to control (5.6 +/- 1.4 pM; p < 0.05). The serum T4 levels were 1.3 times higher in 50 mg/kg BW amiodarone-treated mice (13.2 +/-1.6 pM) compared with the control (10.3 +/- 1.3 pM; p < 0.005). Determination of TRalpha1, alpha2, beta1, and beta2 mRNA in the heart were performed by reverse transcriptase-polymerase chain reaction (RT-PCR)/enzyme-linked immunosorbent assay (ELISA). Both in treated and untreated mice, TRalpha2 mRNA had the highest density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in comparison to the control. There were, however, no differences in the TRalpha2 and TRbeta2 mRNA levels in the mice heart treated with different doses of amiodarone in comparison with the control group. In conclusion, this study shows that amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium in a dose-dependent manner. These results support a thyroid hormone-dependent action of amiodarone.
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PMID:Thyroid hormone alpha1 and beta1 receptor mRNA are downregulated by amiodarone in mouse myocardium. 1044 78

To understand better the mechanisms by which thyroid hormone can exert its effects on the hair follicle, we looked for the expression of members of the thyroid hormone receptor (TR) family in human hair follicles. Immunoreactive TRs were detected in both dermal and epithelial compartments of the human pilosebaceous unit. Using reverse transcriptase-polymerase chain reaction, we established that TRbeta1 was the predominant form of TR expressed in the human hair follicle. In addition, we investigated the effects of 3,3', 5-triiodo-L-thyronine (T3) on the survival of human hair follicles in vitro, to understand the role of this thyroid hormone on hair follicle homeostasis. A physiological level of free T3 significantly enhanced human hair survival in vitro.
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PMID:Thyroid hormone receptor beta1 is expressed in the human hair follicle. 1079 10

Maternal thyroid hormone is transferred to the fetus early in pregnancy and is postulated to regulate brain development. Thyroid hormone nuclear receptor (TR) proteins are present in fetal brain, but their isoformal composition is unknown. We therefore investigated the ontogeny of TR isoforms and related splice variants in first trimester human fetal brain (n = 9) by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. Expression of the TRbeta1, TRalpha1 and c-erbAalpha2 isoforms was detected from 8.1 weeks gestation (wg). An additional truncated species was detected with the c-erbAalpha2 primer set, consistent with the c-erbAalpha3 splice variant previously described in the rat. All c-erbAalpha-derived transcripts were co-ordinately expressed and increased (ca. 8-fold) between 8.1 and 13.9 wg. A more complex ontogenic pattern was observed for TRbeta1, suggestive of a nadir between 8.4 and 12.0 wg. These findings point to an important role for the TRalpha1 isoform in mediating maternal thyroid hormone action during first trimester human fetal brain development.
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PMID:Thyroid hormone receptor gene expression in first trimester human fetal brain. 1090 17

Peroxisome proliferator-activated receptors (PPARs) are pleiotropic regulators of growth and differentiation of many cell types. We have performed a comprehensive analysis of the expression of PPARs, transcriptional cofactors, and marker genes during differentiation of normal human keratinocytes using a combination of reverse transcriptase polymerase chain reaction, Northern and Western blotting, and immunohistochemistry. PPARdelta was the predominant PPAR subtype in human keratinocytes and highly expressed in basal cells and suprabasal cells. Induction of PPARalpha and PPARgamma expression was linked to differentiation, and accordingly, expression of PPARalpha and PPARgamma was in essence confined to suprabasal cells. Differentiation was not accompanied by significant changes in the expression of the coactivators CREB-binding protein, p300, steroid receptor coactivator 1, or the corepressors nuclear receptor corepressor and silence mediator for retinoid and thyroid hormone receptors. We critically evaluated the effects of selective PPAR ligands and a synthetic fatty acid analog, tetradecylthioacetic acid. Tetradecylthioacetic acid activated all human PPAR subtypes in the ranking order PPARdelta >> PPARalpha > PPARgamma. All selective PPAR ligands marginally induced transglutaminase-1 expression with the PPARdelta-selective ligand L165041 being the most potent. The PPARalpha- and PPARgamma-selective ligands Wy14643 and BRL49653 had negligible effect on involucrin expression, whereas a dose-dependent induction was observed with L165041. Simultaneous addition of L165041 and BRL49653 synergistically induced strong involucrin expression. Additionally, L165041 potently induced CD36 mRNA expression. Administration of tetradecylthioacetic acid resulted in a dramatic decrease in proliferation and a robust upregulation of the expression of involucrin and transglutaminase. Our results indicate that tetradecylthioacetic acid may affect keratinocyte gene expression and differentiation via PPAR-dependent and PPAR-independent pathways, and that the latter play an important role.
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PMID:Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. 1134 58

In this work we have extended our initial molecular studies of a consanguineous family with two affected goitrous siblings (H.S.N. and Ac.S.N.) with defective thyroglobulin (Tg) synthesis and secretion because of a homozygotic deletion of a fragment of 138 nucleotides (nt) in the central region of the Tg mRNA, identified previously in H.S.N. In order to identify the intron/exon boundaries and to analyze the regions responsible for pre-mRNA processing corresponding to a 138 nt deletion, we performed a screening of a human genomic library. The intron/exon junction sequences were determined from one positive clone by sequencing both strands of the DNA template. The results showed that the deletion mapped between positions 5549 and 5686 of the Tg mRNA and corresponded to exon 30. The positions of the exon limits differed by three nucleotides from the previously reported data obtained from direct sequencing of the deleted reverse transcriptase-polymerase chain reaction fragment from H.S.N. These variations are because the intron/exon junctions in this region were not available at the time when the deletion was first described. The deletion does not affect the reading frame of the resulting mRNA and is potentially fully translatable into a Tg polypeptide chain that is shortened by 46 residues. The same 138 nt deletion was observed in reverse transcriptase-polymerase chain reaction studies performed in the thyroid tissues from Ac.S.N. Genomic DNA analysis showed that a G to T transversion was observed at position +1 in the donor site of intron 30. Both affected patients (H.S.N. and Ac.S.N.) are homozygous for the mutation whereas the normal sister (At.S.N.) had a normal allele pattern. The functional consequences of the deletion are related to structural changes in the protein molecule that either could modify the normal routing of the translation product through the membrane system of the cell or could impair the coupling reaction. Probably the mutant Tg polypeptide might be functionally active in the production of thyroid hormone, because in the presence of a normal iodine ingestion (approximately 150 microg/day), Ac.S.N. was able to maintain normal serum levels of total triiodothyronine (T3) associated with relatively low serum total thyroxine (T4) with normal somatic development without signs of brain damage.
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PMID:Congenital goiter with hypothyroidism caused by a 5' splice site mutation in the thyroglobulin gene. 1148 98

Thyroid hormone plays a major role in the regulation of bone metabolism but the mechanism by which this is accomplished is not clear. Interactions of thyroid hormone with the growth hormone/insulin-like growth factors (IGFs) axis suggest an alternate pathway of action for triiodothyronine (T(3)) on bone formation, besides direct effects. The present study investigates the influence of T(3) on IGF-1, IGF-2, IGF-1 receptor (IGF-1R), and IGF binding protein (IGFBP) transcripts, and on IGF-1 action in human osteoblastic cells (hOB) under serum-free culture conditions. No influence of T(3) on IGF-1, IGF-2, IGFBP-3, or IGFBP-4 mRNA levels in hOB was observed. However, T(3) at concentrations of 10(-8) mol/L and 10(-7) mol/L increased IGF-1R mRNA levels in a dose-dependent manner (p < 0.01) and enhanced IGFBP-5 mRNA levels at a concentration of 10(-7) mol/L (p < 0.05), as assessed by reverse transcriptase-polymerase chain reaction. Correspondingly, Scatchard analysis of [(125)I]-IGF-1 binding revealed that T(3) at 10(-7) mol/L increased the number of IGF-1 binding sites in hOB, with small changes in receptor affinity. In addition, a synergistic effect of T(3) and IGF-1 on hOB proliferation was found (p < 0.05). We conclude that IGF-1R and IGFBP-5 are thyroid hormone target genes in human osteoblasts, whereas IGF-1 mRNA expression itself appears not to be regulated by T(3) in hOB. However, T(3) stimulates IGF-1R mRNA expression as well as IGF-1 binding and IGF-1 induced cell proliferation in osteoblasts, thus suggesting thyroid hormone may potentiate the effect of IGF-1 at the receptor level. This may contribute to the positive effects of thyroid hormone on bone formation, which, in addition, may be modulated by increased IGFBP-5 expression.
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PMID:Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro. 1172 24

Resistance to thyroid hormone (RTH) is a clinical syndrome characterized by elevated serum thyroid hormone (TH) levels, unsuppressed thyrotropin (TSH) levels, and tissue hyposensitivity to TH. In almost all cases, the genetic basis of RTH lies in mutation of one of the two TH receptor beta (TRbeta) alleles. Recently, patients from several families with phenotypic manifestations of RTH in the absence of TR mutations have been described. We report a case of a 31-year-old woman who presented with goiter, tachycardia, elevated TH levels, unsuppressed TSH, and "inappropriately normal" levels of peripheral TH action markers. In two separate clinical evaluations, the patient exhibited typical clinical and biochemical evidence for peripheral and pituitary RTH. Surprisingly, reverse transcriptase-polymerase chain reaction (RT-PCR) of full-length TRalpha and TRbeta mRNAs, and genomic PCR using primers flanking exons encoding the carboxy-terminal region of TRbeta failed to demonstrate mutations in the TRalpha or TRbeta genes. It is likely that defects in the regulation of TR genes or mutations in transcriptional cofactors involved in TR signaling account for this patient's phenotype.
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PMID:Resistance to thyroid hormone in a patient without thyroid hormone receptor mutations. 1183 36


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