Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal and thyroid hormone-regulated expression of constructs containing varying lengths of 5' flanking sequence of the human glycoprotein hormone alpha subunit gene ligated to the reporter gene encoding chloramphenicol acetyl transferase (CAT) were examined in transfected pituitary GH3 cells. CAT gene expression was quantified by measurement of CAT enzyme activity. In addition, an RNase protection assay was used to confirm changes in CAT mRNA levels and to verify regulation of transcription from the authentic alpha gene start site. The pattern of basal alpha promoter activity indicated the presence of inhibitory DNA elements between -98 and -172 and upstream of -846 relative to the transcriptional start site, as well as a stimulatory element between -346 and -846. Each of the transfected constructs exhibited tri-iodothyronine inhibition of alpha promoter activity, suggesting the presence of an inhibitory thyroid hormone response element within 98 bp of the alpha gene transcriptional start site.
J Mol Endocrinol 1990 Apr
PMID:Multiple DNA elements determine basal and thyroid hormone regulated expression of the human glycoprotein alpha subunit gene in pituitary cells. 169 80

The anterior pituitary contains multiple distinct endocrine cell types that secrete individual hormones. To derive a pure cell culture population in which to study the regulation of the alpha-subunit of TSH free of other hormones and cell types, we have developed a clonal continuous cell line from the transplantable thyrotrope tumor MGH101A. This cell line expresses alpha-subunit mRNA, secretes alpha-subunit protein, and has maintained a stable phenotype for over 3 yr in culture. However, as is the case for the transplantable tumor from which they are derived, these cells do not express the beta-subunit of TSH or respond to TRH or thyroid hormone. We have used this cell line to investigate regulation of the alpha-subunit mRNA by the second messengers, cAMP and phorbol esters, and by glucocorticoids. Phorbol esters increase alpha-subunit mRNA levels significantly (3.5-fold), as does cAMP (1.8-fold). In contrast, glucocorticoids decrease mRNA levels from cAMP-induced or basal levels (2-fold). These cells should prove valuable for study of alpha-subunit gene expression in an isolated renewable clonal cell culture system.
Mol Endocrinol 1990 Apr
PMID:An alpha-subunit-secreting cell line derived from a mouse thyrotrope tumor. 170 2

Thyroid hormones are responsible for the specific biochemical and structural changes that occur during amphibian metamorphosis. In this study we screened a series of cDNAs from a library constructed from T4-treated premetamorphic tadpole liver poly(A)+ RNA in order to identify a clone that could be used to study the influence of T3 on liver-specific gene expression during Rana catesbeiana metamorphosis. The cDNA from one clone exhibited a greater degree of hybridization to liver RNA from thyroid hormone-treated tadpoles than untreated tadpoles and no hybridization to RNA from tail fins of tadpoles of either group. On Northern blots, the mRNA to which the cDNA hybridized was 2.3 kilobases in size. The pattern of hybridization to genomic DNA digested by various restriction enzymes was consistent with the presence of a single gene. Using slot blot analysis we found that the mRNA levels first rose above basal levels only after 5 days of immersion of tadpoles in 12.5 micrograms/liter T3. The mRNA levels increased approximately 10-fold after 7 and 9 days of treatment. Frog livers had mRNA levels that were intermediate between those in untreated tadpoles and tadpoles immersed in T3 for 7 days. Sequence analysis revealed a significant degree of homology to serum albumin and alpha-fetoprotein. While it is known that serum albumin levels rise dramatically during metamorphosis in Rana species, presumably playing a critical role in maintaining water and electrolyte balance during the animals' terrestrial phase, the molecular basis of the induction has not been fully explained.
Mol Endocrinol 1990 Oct
PMID:Cloning and thyroid hormone regulation of albumin mRNA in Rana catesbeiana tadpole liver. 170 84

We have previously demonstrated that binding of in vitro synthesized thyroid hormone receptor (TR) to thyroid hormone response elements (TREs) is enhanced by the addition of nuclear extracts from several different cell types, suggesting that binding of TR is partially dependent on a T3 receptor auxiliary protein (TRAP). We have used the avidin-biotin complex DNA-binding assay to discriminate between regions of TREs that bind TR alone and sites that are influenced by interactions with TRAP. Mutations in the TREs from rat GH and glycoprotein hormone alpha-subunit genes show that a specific DNA sequence is required for TRAP-mediated enhancement of TR binding. Mutations in the B half-site of the rat GH TRE or in similar sequences [(T/A)GGGA] in the alpha-subunit TRE ablate the enhancement of TR binding by TRAP. Furthermore, binding of TR to a natural half-site in the TSH beta-subunit gene (bases -16 to 6), which lacks an additional AGGGA-like sequence, is not enhanced by the addition of TRAP. Binding of TR to TREs was also tested at physiological salt concentrations in the avidin-biotin complex DNA-binding assay. Binding of human TR beta to TREs decreases dramatically at 140 mM KCl compared to binding at 50 mM KCl; however, the addition of TRAP enhances the binding to almost 4-fold of basal binding, suggesting that TRAP may be important for stabilization of TR binding to TREs in the cell.
Mol Endocrinol 1991 Jan
PMID:3,5,3'-triiodothyronine receptor auxiliary protein (TRAP) enhances receptor binding by interactions within the thyroid hormone response element. 170

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.
Mol Endocrinol 1991 Feb
PMID:Effects of neonatal hypothyroidism on rat brain gene expression. 171 32

The three-dimensional structure of the thyroid hormone metabolite, 3,3'-diiodo-L-thyronine (3,3'-T2), complex with human serum transthyretin (TTR) has been refined to R = 18.5% for 8-2 A resolution data. This is the first detailed description of a thyroid hormone metabolite binding to a thyroid transport protein. The four TTR monomeric subunits form a tetramer in the same manner as the native transthyretin reported earlier (Blake, C. C. F., Geisow, M. J., Oatley, S. J., Rerat, B., and Rerat, C. (1978) J. Mol. Biol. 121, 339-356). The two hormone binding sites of the TTR tetramer are occupied by 3,3'-T2. A statistical disorder model for the ligand was applied with a 50% occupancy to account for the discrepancy between the crystallographic 2-fold symmetry of the binding sites and the lack of such symmetry for 3,3'-T2. The bound metabolite has an overall transoid conformation with the either bridge intermediate between skewed and perpendicular. The hormone metabolite is bound 3.5 A deeper and with a different orientation in the channel than observed for thyroxine (T4), thereby revealing the presence of another set of halogen binding sites close to the center of the tetramer. When compared with the binding of T4, these data show that the 3-iodine of 3,3'-T2 occupies the same site as the 3'-iodine of T4, and the metabolite 3'-iodine occupies the water site observed in the T4 complex. The binding affinity of 3,3'-T2, which is 100-fold lower than that of T4, reflects the lack of the second pair of iodine atoms interacting in the channel. In order to understand the tighter binding of T4 observed in the Ala-109----Thr mutant, modeling studies were carried out that indicate that this modification could shorten the contacts between thyroid hormone iodines and residues 108-110 of the binding site.
 ...
PMID:Mechanism of molecular recognition. Structural aspects of 3,3'-diiodo-L-thyronine binding to human serum transthyretin. 173 Jun 1

Previous studies have demonstrated that in different cardiac preparations action potential duration (APD) increases with age. As in various species, thyroid hormone levels increase developmentally, and since hyperthyroidism shortens APD while hypothyroidism prolongs it, we hypothesized that developmental changes in APD result from age-related variations in the thyroid state. The hypothesis was tested by analysing ventricular action potentials and total T4 (TT4) levels in guinea-pigs in the age range of 0 days to 3 months (adult), and in hyperthyroid and hypothyroid newborns (0-5 days old). We found that APD50 increased exponentially with age with a time constant of 6.7 days, from 100.6 +/- 3.4 ms in newborns (0-5 days old) to 147.4 +/- 5.2 ms in adults (P less than 0.001). TT4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 +/- 0.4 micrograms/dl in newborns to less than 1.0 microgram/dl in adults. In the age range studied, APD50 and TT4 were linearly correlated: Y = -12.13X + 142, r - 0.865. In contrast to the marked changes in APD, resting potential and action potential amplitude were age-independent, and Vmax only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT4 = 3.9 +/- 0.4 micrograms/dl), hypothyroid (TT4 = 1.6 +/- 0.4 micrograms/dl) and hyperthyroid (TT4 = 39.8 +/- 10.8 micrograms/dl) newborns, APD50 was: 100.6 +/- 3.4 ms, 117.7 +/- 4.2 ms and 63.7 +/- 7.4 ms, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1991 Jul
PMID:Developmental changes in ventricular action potential properties in guinea-pigs are modulated by age-related changes in the thyroid state. 179 30

In the 40 years of transferrin research, no previous role for apotransferrin has been recognized other than to serve as a plasma carrier for dietary and storage iron. Our studies have revealed a new 'autocrine' growth role for this molecule as well as a possible new cell-cell bridge/CAM function. Certainly, these observations have opened many new areas of investigation both with regard to thyroid hormone action and the function of apotransferrin. In addition, there is now accessible the broader question of tissues other than pituitary which might utilize apotransferrin to regulate responsiveness to thyroid hormones.
Mol Cell Endocrinol 1991 May
PMID:Thyroid hormone regulation of rat pituitary tumor cell growth: a new role for apotransferrin as an autocrine thyromedin. 181 90

We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone family (retinoic acid, 17 beta-estradiol, triiodothyronine, and dexamethasone) was examined. We found that the other hormones alone had no effects on medium osteocalcin and osteocalcin mRNA concentrations by 96 h of treatment. Compared with 1,25(OH)2D3, however, the combination of 1,25(OH)2D3 with dexamethasone resulted in a greatly reduced medium osteocalcin concentration. Also estradiol and triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. In contrast, the combination of 1,25(OH)2D3 with retinoic acid resulted in an increased medium osteocalcin concentration. The inhibition of osteocalcin synthesis by dexamethasone and triiodothyronine was accompanied by decreased osteocalcin mRNA levels. Retinoic acid and estradiol, however, did not influence the 1,25(OH)2D3-induced osteocalcin mRNA levels. To examine the specificity of the hormonal effects, the activity of alkaline phosphatase was determined. Both baseline and 1,25(OH)2D3-stimulated alkaline phosphatase activity was found to be inhibited by all other hormones. These results suggest that the steroidal hormones specifically affect osteocalcin synthesis in osteoblastic bone cells, and that complex interactions occur at the level of transcription and/or translation resulting in each case in a finely adjusted rate of osteocalcin synthesis.
Mol Cell Endocrinol 1991 Apr
PMID:Modulation of 1,25(OH)2D3-induced osteocalcin synthesis in human osteosarcoma cells by other steroidal hormones. 182 Sep 70

The Ah receptor is a presumed member of the superfamily of steroid/thyroid hormone receptors, a trace soluble protein present in a wide variety of vertebrate species that mediates the biological effects of halogenated aromatic hydrocarbons. In this paper, we report the purification to homogeneity of this protein (from the liver of C57BL/6J mice) and its N-terminal amino acid sequence. Selective covalent labeling of the Ah receptor in hepatic cytosol with the photoaffinity ligands 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin simplified identification and quantitation of the receptor and permitted purification under denaturing conditions. Photoaffinity-labeled hepatic cytosol was applied to a phosphocellulose column at 80 mM NaCl, and the fraction enriched with the Ah receptor eluted with 225 mM NaCl. The eluate was diluted to 150 mM NaCl and applied to a DEAE-cellulose column, and the enriched fraction eluted with 300 mM. These two ion exchange chromatography steps usually gave approximately 100-fold enrichment and 40-50% recovery of Ah receptor. The dilute protein in the eluate was precipitated with n-propanol/trichloroacetic acid and solubilized in formic acid. The sample was then subjected to three successive rounds of high performance liquid chromatography on C4 reverse phase columns. The final, shallow-gradient chromatography was able to resolve the unlabeled 95-kDa receptor protein from the later eluting 125I-photoaffinity-labeled protein. The pooled high performance liquid chromatography fractions subjected to electrophoresis on sodium dodecyl sulfate-polyacrylamide gels contained only the 95-kDa band upon staining with Coomassie blue R250 or silver. Using the above protocol, the Ah receptor was purified greater than 150,000-fold, to apparent homogeneity, with an overall yield of 3-5%. The N-terminal amino acid sequence of the purified peptide was determined to be ala/asp-ser-Arg-Lys-arg-Lys-Pro-Val-Gln-Lys-Thr-Val-Lys-Pro-Ile-Pro-Ala- Glu-Gly--Ile-Lys-ser-Asn-Pro-ser-Lys- (where the lowercase indicates a residue determined with less confidence).
Mol Pharmacol 1991 Jan
PMID:Purification and N-terminal amino acid sequence of the Ah receptor from the C57BL/6J mouse. 184 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>