Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotropin receptor (TSHR) mRNA expression has previously been detected in human heart, suggesting a possible role for the receptor in cardiac function and pathophysiology. In the present study we examined the regional distribution of TSHR mRNA in pig heart to map potential cardiac sites of TSH action. Polyadenylated mRNA extracted from thyroid, atria, ventricles, aorta, coronary arteries, epicardial fat, and purified preparations of atrial and ventricular cardiomyocytes was subjected to reverse-transcriptase polymerase chain reaction (RT-PCR) using primers designed to amplify a 311 base pair (bp) DNA segment of the human TSHR. After reverse transcription of 100 ng mRNA, cDNA was amplified by PCR using TSHR primers and compared by electrophoresis on 2% agarose gels. Relative levels of TSHR cDNA (normalized to glyceraldehyde 3-phosphate dehydrogenase [GAPDH]) were as follows: Coronary arteries, epicardial fat > right atrium > left atrium > right ventricle, aorta > left ventricle, ventricular cardiocytes. In contrast to ventricular cardiocytes, purified atrial cardiocytes expressed levels of TSHR mRNA readily detectable with RT-PCR. These findings demonstrate that TSHR mRNA expression in porcine heart varies regionally, and furthermore suggest that areas of highest expression (coronary arteries, adipose tissue, right atrium) are potential sites for a functional or pathologic role of the TSHR.
Thyroid 1997 Aug
PMID:Differential expression of thyrotropin receptor mRNA in the porcine heart. 929 56

Elucidation of the regulation of human sodium-iodide symporter (hNIS) gene expression is critical to understanding its effects on iodide concentration abilities of thyroid and thyroid carcinomas. To explore this issue, a 1.2-kb portion of the 5'-flanking region of the hNIS gene was isolated and characterized. Transient transfections with chimeric luciferase-reporter constructs into a differentiated human thyroid cell line, KAT-50, as well as non-thyroidal cells, defined an active promoter with tissue-specificity. Reverse-transcriptase polymerase chain reaction analysis for hNIS mRNA expression in normal human tissues was positive in thyroid, salivary gland, omentum, and gallbladder. KAT-50 cells expressed hNIS mRNA and were capable of thyrotropin-responsive iodide uptake in vitro. Despite the failure to exhibit iodide concentration in clinical anaplastic carcinoma tumors, 4 of 5 cell lines from this cancer phenotype expressed hNIS mRNA. Definition of the active promoter provides further insights and tools to uncover new approaches to use of radioiodine for therapy of thyroid carcinomas.
Thyroid 1998 Jan
PMID:Cloning of the human sodium-iodide symporter promoter and characterization in a differentiated human thyroid cell line, KAT-50. 949 56

Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 microM Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 microM and 10 microM) or PTU (10 microM and 100 microM) for 2 days caused a significant increase in cellular TPO activity; 100 microM MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction.
Thyroid 1999 May
PMID:Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles. 1036 84

Thyroid hormone (T(3)) has previously been shown to regulate visual function in experimental animals and humans. To determine if T(3) exerts direct effects on retinal function, cultured human fetal retinal pigment epithelial (RPE) cells were tested for the presence of thyroid hormone receptors (TRs) and T(3) responses. Using TR-isoform-specific reverse-transcriptase polymerase chain reaction techniques, mRNA was detected for alpha1, alpha2 and beta1 TR isoforms. Immunohistochemistry using a polyclonal antibody that simultaneously recognizes alpha1, alpha2 and beta1 TRs showed nuclear staining of the fetal RPE. Specific binding of (125)I-T(3) to RPE cell nuclear extracts was detected, and Scatchard analysis revealed a K(d) of 110 pM. To determine if RPE cells can respond to T(3), hyaluronic acid (HA) levels in cell culture media were measured after 2, 4 or 6 days of growth in medium containing 10(-7) M T(3). T(3) inhibited accumulation of HA in the cell culture medium of RPE cells. This effect was not evident at 2 days, but at 4 days there was 42.8% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.01, t test). The effect persisted through 6 days, when there was 46.3% less HA in cell culture medium of RPE cells grown in 10(-7) M T(3) (p < 0.001, t test). The data indicate that human fetal RPE cells are a direct target for thyroid hormones.
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PMID:The human fetal retinal pigment epithelium: A target tissue for thyroid hormones. 1047 68

We have recently shown that the rat hepatic lectin (RHL)-1 subunit of the asialoglycoprotein receptor (ASGPr) is expressed in the PC C13 differentiated thyroid cell line. To investigate in vivo the expression of RHL-1 and the ability of thyrotropin (TSH) to modulate its expression, reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot assays have been performed on thyroid extracts from rats treated with thyroxine (T4) or propylthiouracil (PTU), each of which modulates TSH levels. It is shown that RHL-1 expression is down-regulated by T4 (which decreases serum TSH) and upregulated by PTU (which increases serum TSH), at both mRNA and protein levels. The sensitivity of RHL-1 to neoplastic transformation of thyroid cells has been investigated. The RHL-1 expression pattern has been studied in PC C13 thyroid cells transformed by several oncogenes that induce different degrees of malignancy and dedifferentiation. RT-PCR and Western blot assays show that RHL-1 expression progressively decreases as PC C13 cells acquire a more transformed phenotype. Expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, a housekeeping gene used as internal control to normalize RHL-1 mRNA content, exhibits no variations in the different PC C13 cell lines used. In addition, we show that both native and asialo-thyroglobulin (Tg) bind RHL-1 in vitro, and native Tg binds RHL-1 on the surface of PC C13 cells. After thyroid cells transformation, the surface expression of RHL-1 is inhibited in a measure that correlates with the mRNA and protein levels. Therefore, the RHL-1 inhibition at the mRNA, protein and plasma membrane expression follows a gradient that parallels the progressive acquisition of the fully transformed phenotype in the PC C13 system. The results reported in the present article, together with our previous data, suggest that RHL-1 expression could be regulated, at least in part, by the same transcription factors involved in the expression of the other molecules characteristic of the thyroid differentiated state.
Thyroid 2000 Mar
PMID:The rat hepatic lectin-1 subunit of the asialoglycoprotein receptor is upregulated by thyrotropin and downregulated by neoplastic transformation of thyroid cells. 1077 34

Thyroid stimulating hormone (TSH) is produced by the anterior pituitary and is used to regulate thyroid hormone output, which in turn controls metabolic activity. Currently, the pituitary is believed to be the only source of TSH used by the thyroid. Recent studies in mice from our laboratory have identified a TSHbeta isoform that is expressed in the pituitary, in peripheral blood leukocytes (PBL), and in the thyroid. To determine whether a human TSHbeta splice variant exists that is analogous to the mouse TSHbeta splice variant, and whether the pattern of expression of the splice variant is similar to that observed in mice, PCR amplification of RNAs from pituitary, thyroid, PBL, and bone marrow was done by reverse-transcriptase PCR and quantitative realtime PCR. Human pituitary expressed a TSHbeta isoform that is analogous to the mouse TSHbeta splice variant, consisting of a 27 nucleotide portion of intron 2 and all of exon 3, coding for 71.2% of the native human TSHbeta polypeptide. Of particular interest, the TSHbeta splice variant was expressed at significantly higher levels than the native form or TSHbeta in PBL and the thyroid. The TSHalpha gene also was expressed in the pituitary, thyroid, and PBL, but not the BM, suggesting that the TSHbeta polypeptide in the thyroid and PBL may exist as a dimer with TSHalpha. These findings identify an unknown splice variant of human TSHbeta. They also have implications for immune-endocrine interactions in the thyroid and for understanding autoimmune thyroid disease from a new perspective.
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PMID:A novel thyroid stimulating hormone beta-subunit isoform in human pituitary, peripheral blood leukocytes, and thyroid. 1936 10