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:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormones and their receptors (TRs) have critical functions in development. Here we show that a chicken TR beta cDNA clone encodes a receptor with a novel, short N-terminal domain. In vitro-expressed TR beta protein bound thyroid hormone with similar affinity as the chicken TR alpha. Comparison of expression of TR alpha and TR beta mRNAs throughout chicken development until 3 weeks post-hatching revealed ubiquitous expression of TR alpha mRNAs (in 14 different tissues) with some variations in levels, from early embryonic stages. In contast, expression of TR beta mRNA was restricted, occurring notably in brain, eye, lung, yolk sac and kidney, and was subject to striking developmental control, especially in brain where levels increased 30-fold upon hatching. Levels also sharply increased in late embryonic lung, but were relatively high earlier in embryonic eye and yolk sac. RNase protection analyses detected no obvious mRNAs for alpha and beta TRs with variant C-termini as demonstrated previously for the rat TR alpha gene. The data suggest a general role for TR alpha and specific developmental functions for TR beta, and that thyroid-dependent development involves temporal and tissue-specific expression of the TR beta gene.
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PMID:Contrasting developmental and tissue-specific expression of alpha and beta thyroid hormone receptor genes. 197 Feb 96

Thyroid hormones suppress transcription of the gene for the beta-subunit of thyrotropin (TSH beta). Since the TSH beta gene in both the mouse and the rat contains two start sites of transcription in exon 1, we have investigated whether expression of the gene from each start site is differentially regulated by thyroid hormones in each species. RNase protection analysis was used to assay the levels of mRNA specifically transcribed from the upstream (TSS 1) and downstream (TSS 2) transcription start sites in the mouse and rat pituitary. In euthyroid and hypothyroid pituitaries there was an approximately 5-fold and 2-fold greater abundance of mRNA derived from TSS 2 than TSS 1, respectively. Hypothyroidism induced an 18- and a 9-fold increase in TSH beta gene expression from TSS 1 and TSS 2, respectively. Treatment of hypothyroid animals for 1 day with triiodothyronine (T3) reduced expression from both start sites by about 50%; after 4 days of T3 treatment, TSH beta mRNAs derived from both start sites were below detectable levels. These results were confirmed in the rat by primer extension analysis. Expression from TSS 1 in the mouse was also shown to be dependent on thyroid status using the polymerase chain reaction (PCR) technique. In contrast to previous results from primer extension studies, PCR analysis demonstrated that alternative splicing of the TSH beta RNA primary transcript can occur when transcription is initiated at the upstream start site. We conclude that, in both the mouse and the rat pituitary, expression of the TSH beta gene from both transcription start sites is regulated by thyroid hormones.
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PMID:Thyroid hormone regulates expression of the thyrotropin beta-subunit gene from both transcription start sites in the mouse and rat. 221 30

We examined the effects of thyroid-stimulating hormone (TSH) on basic fibroblast growth factor (basic FGF) expression in isolated ovine thyroid follicles in vitro, and the effects of exogenous basic FGF on thyroid growth and function, to elucidate the significance of increased basic FGF expression during TSH-induced rat thyroid hyperplasia in vivo. Primary cultures of ovine thyroid follicles were maintained in serum-free Ham's modified F-12M medium containing transferrin, somatostatin, and glycyl-histidyl-lysine (designated 3H) with or without basic FGF alone, or in combination with TSH (100 microU/mL) and cortisol (10 nM). Following 48 h incubation, cells were harvested and total RNA prepared for the detection of basic FGF mRNA using Northern blot analysis and ribonuclease protection assay. Basic FGF in the cytoplasm and extracellular matrix fractions was quantified by radioimmunoassay. Basic FGF mRNA transcripts of 3.7, 3.0, and 2.2 kb, respectively, were found in thyroid follicles cultured in 3H medium, and the abundance of each increased between 2- and 3-fold following incubation with 10-50 microU/mL TSH, although higher concentrations of TSH were less effective. Similar results were seen using a more sensitive ribonuclease protection assay. Cells cultured in control, 3H medium contained 2.4 +/- 0.5 fmol immunoreactive basic FGF/micrograms cell DNA within the cytoplasm and 21.1 +/- 1.5 fmol/micrograms DNA within the extracellular matrix (mean +/- SD, n = 6). A significant increase (p < 0.05) in basic FGF content was seen in both cell compartments following incubation with 50 or 100 microU/mL TSH, while 250 microU/mL was less effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid 1994
PMID:Basic fibroblast growth factor (basic FGF) in isolated ovine thyroid follicles: thyrotropin stimulation and effects of basic FGF on DNA synthesis, iodine uptake and organification, and the release of insulin-like growth factors (IGFs) and IGF-binding proteins. 751 16

Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. Involution of thyroid growth was then observed at 16 weeks, 4 weeks after withdrawal of goitrogens and reversion to a normal diet. Experimental animals quickly became hypothyroid compared with controls and exhibited thyroid hyperplasia (control (n = 10): total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight, means +/- S.D.; experimental (n = 10): T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment). Thyroid growth rate subsequently slowed between 2 and 10 weeks. Messenger RNA for basic fibroblast growth factor (basic FGF) and for the high-affinity FGF receptor, was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for basic FGF and its receptor were detectable in thyroids from control rats at all times, while none was detected in the livers from any animal. Basic FGF and receptor mRNAs increased, and were detected at greatest abundance in hyperplastic thyroids at 1 and 2 weeks respectively, during goitre formation, but subsequently declined in parallel with thyroid growth rate at 4 and 10 weeks. When quantified by radioimmunoassay, basic FGF extracted from thyroids was fivefold greater than in controls after 1 week of goitrogen treatment (control (n = 4): 24 +/- 9 pmol/micrograms DNA; goitre (n = 4): 100 +/- 16 pmol/micrograms DNA; P < 0.05). Basic FGF and FGF receptor mRNAs localized by in situ hybridization predominantly to the epithelial cell population within follicles. Localization by immunohistochemistry demonstrated that basic FGF was present in the thyroids of control rats, and was largely associated with the basement membrane of follicles. During thyroid hyperplasia, increased basic FGF immunoreactivity appeared over the cytoplasm of follicular epithelial cells and was lost from the extracellular matrix. Thyroid involution following removal of goitrogen/low iodine treatment was associated with a decrease in mRNA for basic FGF or its receptor, and a loss of immunoreactive basic FGF from the cytoplasm of follicular cells. These results suggest that autocrine expression of basic FGF and FGF receptor could contribute to thyroid hyperplasia in rats.
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PMID:Increase of basic fibroblast growth factor (FGF) and FGF receptor messenger RNA during rat thyroid hyperplasia: temporal changes and cellular distribution. 793 Oct 5

Transforming growth factor-beta 1 (TGF-beta 1) has been reported to influence the growth rate and iodine uptake and organification in vitro by isolated thyrocytes. We have determined changes in the expression and presence of TGF-beta 1 within the rat thyroid during goitre induction, and subsequent involution following goitrogen withdrawal. Hyperplastic goitres were induced in adult rats by administration of methimazole together with a low iodine diet for up to 12 weeks. Goitrogen-treated rats quickly became hypothyroid compared with controls, and exhibited thyroid hyperplasia and hypertrophy assessed by thyroid weight, and DNA and protein content (control: total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight, mean +/- S.D., n = 10; 2 weeks goitrogen: T4 undetectable, thyroid weight 27 +/- 4 mg/100 g, n = 10). Thyroid growth rate slowed subsequently between 2 and 10 weeks. Messenger RNA for TGF-beta 1 was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for TGF-beta 1 were detected in thyroids from control rats at all time-points, while TGF-beta 1 mRNA was barely detectable in liver. Thyroid TGF-beta 1 mRNA levels substantially and progressively increased at 1 and 2 weeks of goitrogen treatment respectively, and remained above control levels at 4 and 10 weeks. As thyroid involution occurred 4 weeks following goitrogen withdrawal, so thyroid TGF-beta 1 mRNA levels declined. In control animals, the cellular localization of TGF-beta 1 mRNA, determined by in situ hybridization, was found to be a subpopulation of follicular epithelial cells, and immunohistochemical co-localization of TGF-beta 1 and calcitonin identified these tentatively as parafollicular or C-cells. During goitre formation, abundant TGF-beta 1 mRNA and peptide were found to be widely distributed within the entire follicular epithelium. While this ubiquitous distribution had largely disappeared in the involuting gland, TGF-beta 1 peptide was retained within the parafollicular cells, which appeared more abundant than in thyroids from control animals. These results suggest that an increased local expression of TGF-beta 1, a putative growth inhibitor, during thyroid hyperplasia may contribute to the temporal stabilization of goitre size.
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PMID:Enhanced expression of transforming growth factor-beta 1 during thyroid hyperplasia in rats. 801 2

Many postembryonic developmental processes are regulated by an intricate interplay among hormones and growth factors. Thyroid hormone (TH) and estrogen are well known to be individually and obligatorily required for the initiation and progression of amphibian metamorphosis and vitellogenesis. However, whether or not a possible interplay between these two hormones would affect these two developmental processes is not known. Here we report on how triiodothyronine (T3) enhances the precocious activation of vitellogenin (Vit) genes by estradiol (E2) in Xenopus tadpoles during metamorphosis. Using a combination of filter hybridization, RNase protection assay and in situ hybridization, we first show that very low doses (10(-9) M) of exogenous T3 will autoinduce thyroid hormone receptor (TR) mRNA in several tissues of premetamorphic tadpoles. The same treatment enhances and accelerates the precocious activation of the silent vitellogenin genes by E2 at metamorphic climax (stages 60-64) but not before mid-metamorphosis (stages 56-58). This developmental stage dependency may be explained by our finding that, under the same experimental conditions, T3 fails to alter the autoinduction of ER mRNA at mid-metamorphosis but strongly potentiates it at metamorphic climax. Thus a developmental stage specific interplay between thyroid hormone and estrogen determines the kinetics and extent of activation of vitellogenin and estrogen receptor genes during Xenopus postembryonic development.
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PMID:Interplay between thyroid hormone and estrogen in modulating expression of their receptor and vitellogenin genes during Xenopus metamorphosis. 818 48

Thyroglobulin (Tg) provides the peptide backbone for synthesis for thyroid hormones. Because previous studies by various techniques have raised the possibility of heterogeneity in Tg's message and translated protein, we have applied a highly sensitive ribonuclease protection assay (RPA) to examine the mRNA species translating part of Tg's C-terminal region, an area containing three of Tg's hormonogenic sites. Tissue samples were obtained from 18 normal and diseased human thyroids at surgery. Three probes spanning part or all of the nucleotide segment containing bases 7808-8086 in the cDNA sequence, detected full-length mRNAs as the dominant transcripts but also showed the consistent presence of at least seven discrete smaller mRNA species in the thyroid samples. The amounts of these smaller mRNAs varied among tissue samples without a discernible relationship to the underlying clinical thyroid condition. We conclude that the mRNA for this region of Tg is quite heterogeneous and offers potential opportunities for translation of different peptide sequences that might affect hormonogenesis in the C-terminal region of the protein.
Thyroid 1996 Dec
PMID:mRNA encoding human thyroglobulin's C-terminus is heterogeneous. 900 Dec

The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR alpha 1, alpha 1, beta 1 and beta 2 was performed. RA, T3 and DITPA significantly downregulated the alpha 1, beta 1 and beta 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.
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PMID:Downregulation of thyroid hormone receptor subtype mRNA levels by retinoic acid in cultured cardiomyocytes. 946 61

We previously reported that our patients with congenital primary hypothyroidism associated with thyrotropin (TSH) unresponsiveness through an autosomal recessive pattern of inheritance did not have mutations in the coding region of the TSH receptor gene. In the current study, we analyzed the promoter of the TSH receptor gene and the entire region of the thyroid transcription factor-1 (TTF-1) gene, including promoter, two exons, and one intron, because expression of the rat TSH receptor gene is reported to be stimulated by the interaction of the promoter of the TSH receptor gene with TTF-1. Screening for mutations was performed by RNase cleavage assay, and the polymerase chain reaction (PCR) products were subsequently sequenced by the automatic sequencer. In the promoter of the TSH receptor gene, a duplication of nucleotides -346 to -330 was detected in one allele, but haplotype analysis of the family demonstrated lack of linkage between the duplication and the TSH unresponsiveness. The same duplication was also observed in some normal subjects. In the TTF-1 gene, we detected a transition (guanine to adenine) in the intron at the minus four position of cryptic 3' splice site in one allele, but absence of linkage suggested that the transition was not responsible for the TSH unresponsiveness. The same transition also was found in some normal subjects. These results suggest that TSH unresponsiveness in our patients is unlikely to be caused by mutations either in the promoter of the TSH receptor gene or in the TTF-1 gene.
Thyroid 1998 Apr
PMID:Analysis of the promoter of the thyrotropin receptor gene and the entire genomic sequence of thyroid transcription factor-1 in familial congenital hypothyroidism due to thyrotropin unresponsiveness. 958 95

Thyroid hormones influence both bone formation and bone resorption. Clinical data and animal studies provide evidence of skeletal site heterogeneity (hip vs. spine) of bone responses to thyroid hormones. In vitro studies also demonstrate direct effects of thyroid hormones on cells of the osteoblast lineage. Transcriptional regulation by thyroid hormone is mediated by ligand-dependent transcription factors called thyroid hormone receptors (TRs). Two genes, c-ErbAalpha and c-ErbAbeta, generate at least four TR isoforms in the rat: TRalpha(1), c-erbAalpha(2), TRbeta(1), and TRbeta(2). Although functional TRs have been identified in cells of the osteoblast lineage, it is still not known if TR isoform expression in bone differs depending upon which skeletal site is examined. We have used ribonuclease protection assay and Northern blot analysis to simultaneously examine the expression of TR isoform mRNAs in adult rat femoral and vertebral bone. TRalpha(1), c-erbAalpha(2), and TRbeta(1) are expressed in both femur and vertebra whole bone. Bone marrow cells from both skeletal sites were also cultured under conditions whereby the osteoprogenitors differentiated into osteoblasts and formed a mineralized extracellular matrix. TRalpha(1), c-erbAalpha(2), and TRbeta(1) mRNAs are each expressed in both femoral and vertebral osteoblast cultures. The presence of TRalpha(1), c-erbAalpha(2), and beta(1) proteins was confirmed by Western analysis of nuclear protein extracts from femoral and vertebral cell cultures. These results indicate that the three predominant TR isoforms are highly expressed in bone and osteoblasts from femurs and vertebrae. Whether there are distinct mechanisms of thyroid hormone action mediated by TRalpha(1), c-erbAalpha(2), and TRbeta(1) at these separate skeletal sites remain to be shown.
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PMID:Expression of multiple thyroid hormone receptor isoforms in rat femoral and vertebral bone and in bone marrow osteogenic cultures. 1044 Sep 37


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