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Gene Review

Tshb  -  thyroid stimulating hormone, beta subunit

Mus musculus

Synonyms: TSH-B, TSH-beta, Thyroid-stimulating hormone subunit beta, Thyrotropin beta chain, Thyrotropin subunit beta, ...
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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


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


Biological context of Tshb


Anatomical context of Tshb


Associations of Tshb with chemical compounds


Physical interactions of Tshb


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


Analytical, diagnostic and therapeutic context of Tshb


  1. Thyrotropin: an endogenous regulator of the in vitro immune response. Kruger, T.E., Smith, L.R., Harbour, D.V., Blalock, J.E. J. Immunol. (1989) [Pubmed]
  2. Probing the genetic basis for thyrotropin receptor antibodies and hyperthyroidism in immunized CXB recombinant inbred mice. Aliesky, H.A., Pichurin, P.N., Chen, C.R., Williams, R.W., Rapoport, B., McLachlan, S.M. Endocrinology (2006) [Pubmed]
  3. HLA-DR3 Transgenic Mice Immunized with Adenovirus Encoding the Thyrotropin Receptor: T Cell Epitopes and Functional Analysis of the CD40 Graves' Polymorphism. Pichurin, P., Pham, N., David, C.S., Rapoport, B., McLachlan, S.M. Thyroid (2006) [Pubmed]
  4. Hormonal regulation of thyrotropin alpha and beta subunit mRNAs. Gurr, J.A., Vrontakis, M.E., Athanasian, E.A., Wagner, C.R., Kourides, I.A. Horm. Metab. Res. (1986) [Pubmed]
  5. Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system. Abel, E.D., Boers, M.E., Pazos-Moura, C., Moura, E., Kaulbach, H., Zakaria, M., Lowell, B., Radovick, S., Liberman, M.C., Wondisford, F. J. Clin. Invest. (1999) [Pubmed]
  6. The effect of dietary protein on thyrotropin-releasing hormone and thyrotropin gene expression. Shi, Z.X., Levy, A., Lightman, S.L. Brain Res. (1993) [Pubmed]
  7. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Clifton-Bligh, R.J., Wentworth, J.M., Heinz, P., Crisp, M.S., John, R., Lazarus, J.H., Ludgate, M., Chatterjee, V.K. Nat. Genet. (1998) [Pubmed]
  8. Molecular biology of thyrotropin. Shupnik, M.A., Ridgway, E.C., Chin, W.W. Endocr. Rev. (1989) [Pubmed]
  9. Targeted disruption of the pituitary glycoprotein hormone alpha-subunit produces hypogonadal and hypothyroid mice. Kendall, S.K., Samuelson, L.C., Saunders, T.L., Wood, R.I., Camper, S.A. Genes Dev. (1995) [Pubmed]
  10. Negative regulation by thyroid hormone receptor requires an intact coactivator-binding surface. Ortiga-Carvalho, T.M., Shibusawa, N., Nikrodhanond, A., Oliveira, K.J., Machado, D.S., Liao, X.H., Cohen, R.N., Refetoff, S., Wondisford, F.E. J. Clin. Invest. (2005) [Pubmed]
  11. The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim. Chen, C.R., Pichurin, P., Nagayama, Y., Latrofa, F., Rapoport, B., McLachlan, S.M. J. Clin. Invest. (2003) [Pubmed]
  12. Effects of thyroid hormones and thyrotropin-releasing hormone on thyrotropin biosynthesis by mouse pituitary tumor cells in vitro. Cacicedo, L., Pohl, S.L., Reichlin, S. Endocrinology (1981) [Pubmed]
  13. A major role for non-major histocompatibility complex genes but not for microorganisms in a novel murine model of Graves' hyperthyroidism. Nagayama, Y., McLachlan, S.M., Rapoport, B., Niwa, M. Thyroid (2003) [Pubmed]
  14. Identification of separate mRNAs coding for the alpha and beta subunits of thyrotropin. Vamvakopoulos, N.C., Kourides, I.A. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  15. Altered responsiveness to thyrotropin in thyroid slices of Graves' disease preoperatively treated with excess iodide. Onaya, T., Miyakawa, M., Makiuchi, M., Furihata, R. J. Clin. Endocrinol. Metab. (1978) [Pubmed]
  16. A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter. Haugen, B.R., Wood, W.M., Gordon, D.F., Ridgway, E.C. J. Biol. Chem. (1993) [Pubmed]
  17. Synthesis, cloning, and identification of DNA sequences complementary to mRNAs for alpha and beta subunits of thyrotropin. Vamvakopoulos, N.C., Monahan, J.J., Kourides, I.A. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  18. Assignment of the genes for the alpha and beta subunits of thyrotropin to different mouse chromosomes. Kourides, I.A., Barker, P.E., Gurr, J.A., Pravtcheva, D.D., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  19. Cloning of cDNA encoding the pre-beta subunit of mouse thyrotropin. Gurr, J.A., Catterall, J.F., Kourides, I.A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  20. Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin. Abel, E.D., Kaulbach, H.C., Campos-Barros, A., Ahima, R.S., Boers, M.E., Hashimoto, K., Forrest, D., Wondisford, F.E. J. Clin. Invest. (1999) [Pubmed]
  21. An intrinsic thyrotropin-mediated pathway of TNF-alpha production by bone marrow cells. Wang, H.C., Dragoo, J., Zhou, Q., Klein, J.R. Blood (2003) [Pubmed]
  22. Determinants of thyrotrope-specific thyrotropin beta promoter activation. Cooperation of Pit-1 with another factor. Haugen, B.R., McDermott, M.T., Gordon, D.F., Rupp, C.L., Wood, W.M., Ridgway, E.C. J. Biol. Chem. (1996) [Pubmed]
  23. Effect of thyrotropin-releasing hormone on the carbohydrate structure of secreted mouse thyrotropin. Analysis by lectin affinity chromatography. Gesundheit, N., Fink, D.L., Silverman, L.A., Weintraub, B.D. J. Biol. Chem. (1987) [Pubmed]
  24. A mouse monoclonal antibody to the TSHR. Stankowiak-Kulpa, H., Sanders, J., Depraetere, H., Jeffreys, J., Evans, M., Richards, T., Furmaniak, J., Smith, B.R. Arch. Immunol. Ther. Exp. (Warsz.) (2005) [Pubmed]
  25. Normal thyroid structure and function in rhophilin 2-deficient mice. Behrends, J., Clément, S., Pajak, B., Pohl, V., Maenhaut, C., Dumont, J.E., Schurmans, S. Mol. Cell. Biol. (2005) [Pubmed]
  26. INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. Kumagai, J., Hsu, S.Y., Matsumi, H., Roh, J.S., Fu, P., Wade, J.D., Bathgate, R.A., Hsueh, A.J. J. Biol. Chem. (2002) [Pubmed]
  27. Protein factors in thyrotropic tumor nuclear extracts bind to a region of the mouse thyrotropin beta-subunit promoter essential for expression in thyrotropes. Wood, W.M., Ocran, K.W., Kao, M.Y., Gordon, D.F., Alexander, L.M., Gutierrez-Hartmann, A., Ridgway, E.C. Mol. Endocrinol. (1990) [Pubmed]
  28. Bihormonal regulation of the thyrotropin-releasing hormone receptor in mouse pituitary thyrotropic tumor cells in culture. Gershengorn, M.C. J. Clin. Invest. (1978) [Pubmed]
  29. Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter. Gordon, D.F., Lewis, S.R., Haugen, B.R., James, R.A., McDermott, M.T., Wood, W.M., Ridgway, E.C. J. Biol. Chem. (1997) [Pubmed]
  30. Consequences of combined maternal, fetal and persistent postnatal hypothyroidism on the development of auditory function in Tshrhyt mutant mice. Song, L., McGee, J.A., Walsh, E.J. Brain Res. (2006) [Pubmed]
  31. Spatio-temporal expression of TSH beta and FSH beta genes in normally metamorphosing, metamorphosed, and metamorphosis-arrested Hynobius retardatus. Kanki, K., Wakahara, M. Gen. Comp. Endocrinol. (2000) [Pubmed]
  32. The thyrotropin (thyroid-stimulating hormone) receptor is expressed on murine dendritic cells and on a subset of CD45RBhigh lymph node T cells: functional role for thyroid-stimulating hormone during immune activation. Bağriaçik, E.U., Klein, J.R. J. Immunol. (2000) [Pubmed]
  33. The combination of Pit-1 and Pit-1T have a synergistic stimulatory effect on the thyrotropin beta-subunit promoter but not the growth hormone or prolactin promoters. Haugen, B.R., Gordon, D.F., Nelson, A.R., Wood, W.M., Ridgway, E.C. Mol. Endocrinol. (1994) [Pubmed]
  34. Targeted ablation of cells in the pituitary primordia of transgenic mice. Burrows, H.L., Birkmeier, T.S., Seasholtz, A.F., Camper, S.A. Mol. Endocrinol. (1996) [Pubmed]
  35. 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. Abel, E.D., Moura, E.G., Ahima, R.S., Campos-Barros, A., Pazos-Moura, C.C., Boers, M.E., Kaulbach, H.C., Forrest, D., Wondisford, F.E. Mol. Endocrinol. (2003) [Pubmed]
  36. Folding-dependent binding of thyrotropin (TSH) and TSH receptor autoantibodies to the murine TSH receptor ectodomain. Vlase, H., Matsuoka, N., Graves, P.N., Magnusson, R.P., Davies, T.F. Endocrinology (1997) [Pubmed]
  37. Effects of thyrotropin-releasing hormone (TRH) on the actions of pentobarbital and other centrally acting drugs. Breese, G.R., Cott, J.M., Cooper, B.R., Prange, A.J., Lipton, M.A., Plotnikoff, N.P. J. Pharmacol. Exp. Ther. (1975) [Pubmed]
  38. A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor. Nagayama, Y., Kita-Furuyama, M., Ando, T., Nakao, K., Mizuguchi, H., Hayakawa, T., Eguchi, K., Niwa, M. J. Immunol. (2002) [Pubmed]
  39. Artifactual elevation of thyroid-stimulating hormone. Wood, J.M., Gordon, D.L., Rudinger, A.N., Brooks, M.M. Am. J. Med. (1991) [Pubmed]
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