Disease relevance of Tshb

• We have previously shown that thyrotropin (TSH), which is produced by lymphocytes in response to the T cell mitogen staphylococcal enterotoxin A, enhances in vitro antibody production to T cell-dependent and independent Ag (SRBC and trinitrophenylated Brucella abortus [BA-TPN], respectively) as determined by a direct plaque-forming cell assay [1].
• Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice [2].
• HLA-DR3 Transgenic Mice Immunized with Adenovirus Encoding the Thyrotropin Receptor: T Cell Epitopes and Functional Analysis of the CD40 Graves' Polymorphism [3].
• After 3 days of treatment with T3 (0.5 micrograms/100 g body weight) serum TSH, alpha and TSH-beta levels were 77%, 79% and 44% of control, respectively [4].
• Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss [5].

Psychiatry related information on Tshb

• In the rat, 48 h of food deprivation significantly reduces hypothalamic paraventricular nucleus (PVN) thyrotropin-releasing hormone (TRH) gene expression, anterior pituitary thyrotropin (TSH) gene expression and circulating triiodothyronine (T3) [6].

High impact information on Tshb

• Although thyroid hypoplasia has recently been associated with mutations in the thyrotropin (TSH) receptor, the cause of thyroid agenesis is unknown [7].
• Molecular biology of thyrotropin [8].
• This establishes the importance of thyrotropin in ontogeny and reveals that fetal pituitary gonadotropins are not required for sexual differentiation or genital development in male or female fetuses [9].
• Serum thyroxine, T3, and thyroid-stimulating hormone (TSH) levels and pituitary Tshb mRNA levels were inappropriately elevated compared with those of WT animals, and L-T3 treatment failed to suppress serum TSH and pituitary Tshb mRNA levels [10].
• The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim [11].

Chemical compound and disease context of Tshb

• Effects of thyroid hormones and thyrotropin-releasing hormone on thyrotropin biosynthesis by mouse pituitary tumor cells in vitro [12].
• Intramuscular injection of recombinant adenovirus expressing the thyrotropin receptor (AdCMVTSHR) induces Graves'-like hyperthyroidism (thyrotropin receptor [TSHR] antibodies, elevated thyroxine, and diffuse goiter) in more than 50% of female BALB/c mice [13].
• A 9S mRNA, purified from mouse thyrotropic pituitary tumors by sucrose density gradient centrifugation of poly(A)-enriched mRNA, directed the synthesis of only alpha and beta subunits of thyrotropin in the reticulocyte lysate translation system [14].
• Altered responsiveness to thyrotropin in thyroid slices of Graves' disease preoperatively treated with excess iodide [15].

Biological context of Tshb

• Reintroduction of Pit-1 into alpha-TSH cells by transient transfection does not restore TSH beta promoter activity [16].
• Pituitary alpha and TSH-beta mRNA content was estimated by dot blot hybridization of total RNA with 32P-labelled alpha and TSH-beta plasmid probes [4].
• Synthesis, cloning, and identification of DNA sequences complementary to mRNAs for alpha and beta subunits of thyrotropin [17].
• Assignment of the genes for the alpha and beta subunits of thyrotropin to different mouse chromosomes [18].
• Determination of the nucleotide sequence of one cDNA, 595 base pairs in length, allowed us to deduce the entire amino acid sequence of the mouse TSH beta subunit [19].

Anatomical context of Tshb

• Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production [20].
• An intrinsic thyrotropin-mediated pathway of TNF-alpha production by bone marrow cells [21].
• The alpha-TSH cell line, which lacks all Pit-1 proteins, requires both isoforms in order to stimulate TSH beta promoter activity [16].
• Thyrotropin (TSH) beta is a subunit of TSH, the expression of which is limited to the thyrotrope cells of the anterior pituitary gland [22].
• A series of mouse-hamster somatic cell hybrids, containing reduced numbers of mouse chromosomes and a complete set of hamster chromosomes, was used to determine the chromosomal locations of the genes for the alpha and beta subunits of mouse thyrotropin [18].

Associations of Tshb with chemical compounds

• Effect of thyrotropin-releasing hormone on the carbohydrate structure of secreted mouse thyrotropin. Analysis by lectin affinity chromatography [23].
• Thyrotropin (TSH) is a glycoprotein hormone whose secretion from the anterior pituitary is regulated, in part, by the hypothalamic tripeptide thyrotropin-releasing hormone (TRH) [23].
• This enhancement effect by TRH was specifically blocked by rabbit antisera to the TSH-beta subunit, whereas addition of normal rabbit sera had no effect [1].
• There was no change in alpha mRNA after 3 days of T3 treatment but TSH-beta mRNA had decreased to 60% of control [4].
• Estrogen treatment increased serum TSH and subunit levels and TSH-beta mRNA, but not alpha [4].

Physical interactions of Tshb

• The pituitary-specific transcription factor Pit-1 is present in thyrotropes and interacts with three cis-acting elements in the functionally important region of the TSH beta promoter [16].
• INTRODUCTION: Mouse monoclonal antibodies (mAbs) with the ability to inhibit thyrotropin (TSH) binding to the TSH receptor (TSHR) are useful tools to study TSH-TSHR interaction [24].
• Rhophilin 2 is a Rho GTPase binding protein initially isolated by differential screening of a chronically thyrotropin (TSH)-stimulated dog thyroid cDNA library [25].
• Several orphan G protein-coupled receptors homologous to gonadotropin and thyrotropin receptors have recently been identified and named as LGR4-8 [26].
• DNase-I protection studies suggest that there are multiple protein-binding domains in the mouse TSH beta 5' flanking sequence [27].

Regulatory relationships of Tshb

• TRH and T3 interact to control thyrotropin release [28].
• Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter [29].
• Tshrhyt/hyt mutant mice express a point mutation in the gene encoding the thyrotropin receptor, and affected animals are congenitally hypothyroid and profoundly deaf as a consequence when the condition is untreated [30].
• These results suggest that TSH beta overexpression in TU-SPCs must be caused by a deprivation of TH which plays a role in the negative feedback system and that FSH beta expression also might be enhanced by mechanisms similar to those of TSH beta, probably due to certain overlapping of the endocrinological regulation of TSH and FSH in H. retardatus [31].
• However, recombinant TSHbeta was found to significantly enhance the phagocytic activity of dendritic cells from adult animals and to selectively augment IL-1beta and IL-12 cytokine responses of dendritic cells following phagocytic activation [32].

Other interactions of Tshb

• A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter [16].
• When added to GH3 cells, which lack only the Pit-1T isoform, Pit-1T selectively stimulated the TSH beta promoter and not the GH or PRL promoters, suggesting that the thyrotrope-specific Pit-1T exhibits a promoter-specific effect.(ABSTRACT TRUNCATED AT 250 WORDS)[33]
• The absence of detectable transcripts for alpha-subunit, TSH beta-subunit, or LH beta-subunit by in situ hybridization confirmed that ablation was complete [34].
• Dominant inhibition of thyroid hormone action selectively in the pituitary of thyroid hormone receptor-beta null mice abolishes the regulation of thyrotropin by thyroid hormone [35].
• Folding-dependent binding of thyrotropin (TSH) and TSH receptor autoantibodies to the murine TSH receptor ectodomain [36].

Analytical, diagnostic and therapeutic context of Tshb

• RNA was fractionated by agarose gel electrophoresis under denaturing and nondenaturing conditions and transferred to diazobenzyloxymethyl-paper. alpha thyrotropin mRNA of two sizes, 650 and approximately equal to 1500 nucleotides long, were identified [17].
• Plasmids containing cDNA sequences coding for the beta subunit of thyrotropin (TSH) were identified by cell-free translation of hybrid-selected mRNA and immunoprecipitation with specific antibody to TSH beta subunit [19].
• Thyrotropin or L-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital [37].
• A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor [38].
• A clinically euthyroid patient was found to have a normal serum thyroxine level and an elevated plasma thyrotropin (TSH) level measured by fluoroimmunoassay [39].

References