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Gene Review

TSHB  -  thyroid stimulating hormone, beta

Homo sapiens

Synonyms: TSH-B, TSH-BETA, TSH-beta, Thyroid-stimulating hormone subunit beta, Thyrotropin beta chain, ...
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Disease relevance of TSHB


High impact information on TSHB

  • Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non-triodothyronine (T3)-suppressible serum TSH and pituitary TSH-beta mRNA [5].
  • Mutation of a critical carboxy-terminal cysteine residue (C105V) in the thyrotropin-beta (TSH-beta) subunit gene was found in two related families with central hypothyroidism [6].
  • This natural mutation of the TSH-beta subunit confirms the importance of the seat belt in the family of pituitary and placental glycoprotein hormones [6].
  • On the other hand, these agents induced human TSH beta gene expression 4-12-fold in GH3 cells [7].
  • cAMP regulation of the human thyrotropin-beta (TSH beta) gene cAMP was studied in two heterologous cell lines, a human embryonal kidney cell line (293) and a rat pituitary cell line (GH3) [7].

Chemical compound and disease context of TSHB


Biological context of TSHB


Anatomical context of TSHB


Associations of TSHB with chemical compounds

  • In addition, the downstream site overlaps with the recently characterized thyroid hormone-inhibitory element of TSHB [11].
  • Regulation of human thyrotropin beta subunit gene (TSHB) expression by thyrotropin-releasing hormone (TRH) was examined in a clonal rat pituitary-cell line (GH3) [11].
  • The region between the 10th and 12th cysteine (Cys88-Cys105 in human thyroid-stimulating hormone beta-subunit (hTSHbeta)) of the glycoprotein hormone beta-subunits corresponds to the disulfide-linked seat-belt region [20].
  • TRH treatment on pituitary cells increased TSH beta mRNA level, while T4 treatment decreased TSH beta mRNA level [16].
  • Expression of one or more of the glycoprotein hormone genes (alpha, LH beta, FSH beta, TSH beta) was identified most commonly (79%) with expression of multiple beta-subunit genes in many cases [21].

Physical interactions of TSHB

  • Three regions within the 5'-flanking region of the TSH beta gene have A-T-rich sequences which have sequence similarity to binding sites for the pituitary-specific POU domain transcription factor Pit-1/GHF-1 [22].
  • This TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3-dependent negative regulation of both TSHbeta and glycoprotein hormone alpha-subunit genes in cotransfection studies [23].

Co-localisations of TSHB

  • In 7 cases, TSH-beta was positive, and in some cases, TSH-beta was colocalized in the same tumour cells which contained alpha-subunit and FSH-beta subunit [24].

Regulatory relationships of TSHB

  • We suggest that both protein kinases C and A as well as TRH share a common mediator which recognizes the TGGGTCA element in activating the hTSH beta promoter [14].
  • Conversely, introduction of the hTSHbeta seat-belt sequence into hCGbeta generated an hCG chimera that bound to and activated the TSH receptor but not the CG/lutropin (LH) receptor [20].
  • On the other hand, double-staining immunohistochemistry showed that several prolactin (PRL) immunoreactive cells coexpressed TSHbeta within single cells even in normal controls [25].
  • NPY suppressed TSHbeta mRNA level, but stimulated alpha-subunit mRNA level [26].

Other interactions of TSHB

  • Two tumors that contained TSH beta mRNA by RNAse protection assay also contained Pit-1 mRNA [27].
  • We have previously characterized recombinant human TSH (rhTSH) secreted by Chinese hamster ovary cells attached to microcarrier beads in a large scale bioreactor after stable transfection of hCG alpha and hTSH beta minigenes [28].
  • The results allowed localization of TSHB to the proximal portion of 1p22, which is in the region of localization of the linkage group including amylase (AMY), nerve growth factor beta subunit (NGFB), and NRAS, which are conserved in humans and rodents [15].
  • The human thyrotropin beta (hTSH beta) gene is inducible by various agents including thyrotropin-releasing hormone, phorbol esters, or the adenylyl cyclase activator forskolin [14].
  • Replacing the entire seat-belt of hTSHbeta with the hCG sequence conferred full hCG receptor binding and activation to the hTSH chimera, whereas TSH receptor binding and activation were abolished [20].

Analytical, diagnostic and therapeutic context of TSHB


  1. Initially elevated TSH and congenital central hypothyroidism due to a homozygous mutation of the TSH beta subunit gene: case report and review of the literature. Partsch, C.J., Riepe, F.G., Krone, N., Sippell, W.G., Pohlenz, J. Exp. Clin. Endocrinol. Diabetes (2006) [Pubmed]
  2. Immunohistochemical studies of chromogranins (A and C) in pituitary adenomas. Oda, K., Inada, K., Osamura, R.Y. Pathol. Res. Pract. (1991) [Pubmed]
  3. Genetic basis of congenital hypothyroidism: abnormalities in the TSHbeta gene, the PIT1 gene, and the NIS gene. Tatsumi, K., Miyai, K., Amino, N. Clin. Chem. Lab. Med. (1998) [Pubmed]
  4. GH and PRL gene expression by nonradioisotopic in situ hybridization in TSH-secreting pituitary adenomas. Sanno, N., Teramoto, A., Matsuno, A., Takekoshi, S., Osamura, R.Y. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  5. 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]
  6. A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene. Medeiros-Neto, G., Herodotou, D.T., Rajan, S., Kommareddi, S., de Lacerda, L., Sandrini, R., Boguszewski, M.C., Hollenberg, A.N., Radovick, S., Wondisford, F.E. J. Clin. Invest. (1996) [Pubmed]
  7. Role of a pituitary-specific transcription factor (pit-1/GHF-1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression. Steinfelder, H.J., Radovick, S., Mroczynski, M.A., Hauser, P., McClaskey, J.H., Weintraub, B.D., Wondisford, F.E. J. Clin. Invest. (1992) [Pubmed]
  8. Clinical and immunohistochemical studies on TSH-secreting pituitary adenoma: its multihormonality and expression of Pit-1. Sanno, N., Teramoto, A., Matsuno, A., Inada, K., Itoh, J., Osamura, R.Y. Mod. Pathol. (1994) [Pubmed]
  9. Free alpha-subunit and intact TSH secretion in vitro are closely associated in human somatotroph adenomas. Aylwin, S.J., King, A., Blenke, A., Geddes, J.F., Wood, D.F., Monson, J.P., Burrin, J.M. Eur. J. Endocrinol. (1998) [Pubmed]
  10. Thyroid hormone inhibition of human thyrotropin beta-subunit gene expression is mediated by a cis-acting element located in the first exon. Wondisford, F.E., Farr, E.A., Radovick, S., Steinfelder, H.J., Moates, J.M., McClaskey, J.H., Weintraub, B.D. J. Biol. Chem. (1989) [Pubmed]
  11. Thyrotropin-releasing hormone regulation of human TSHB expression: role of a pituitary-specific transcription factor (Pit-1/GHF-1) and potential interaction with a thyroid hormone-inhibitory element. Steinfelder, H.J., Hauser, P., Nakayama, Y., Radovick, S., McClaskey, J.H., Taylor, T., Weintraub, B.D., Wondisford, F.E. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  12. Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), are located less than 310 kb apart in both human and mouse genomes. Dracopoli, N.C., Rose, E., Whitfield, G.K., Guidon, P.T., Bale, S.J., Chance, P.A., Kourides, I.A., Housman, D.E. Genomics (1988) [Pubmed]
  13. Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1. Steinfelder, H.J., Radovick, S., Wondisford, F.E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  14. An AP-1-like factor and the pituitary-specific factor Pit-1 are both necessary to mediate hormonal induction of human thyrotropin beta gene expression. Kim, M.K., McClaskey, J.H., Bodenner, D.L., Weintraub, B.D. J. Biol. Chem. (1993) [Pubmed]
  15. Chromosome regional mapping for the human thyroid stimulating hormone beta subunit (TSHB) gene. Tokino, T., Hayashizaki, Y., Takata, K.I., Yoshida, M.C., Matsubara, K. Cytogenet. Cell Genet. (1990) [Pubmed]
  16. Molecular cloning of cDNA encoding thyroid stimulating hormone beta subunit of bighead carp Aristichthys nobilis and regulation of its gene expression. Chatterjee, A., Hsieh, Y.L., Yu, J.Y. Mol. Cell. Endocrinol. (2001) [Pubmed]
  17. Serum free thyrotropin subunit in congenital isolated thyrotropin deficiency. Miyai, K., Endo, Y., Iijima, Y., Kabutomori, O., Hayashizaki, Y. Endocrinol. Jpn. (1988) [Pubmed]
  18. AP-1 antagonizes thyroid hormone receptor action on the thyrotropin beta-subunit gene. Wondisford, F.E., Steinfelder, H.J., Nations, M., Radovick, S. J. Biol. Chem. (1993) [Pubmed]
  19. Hyperthyroidism due to a pituitary adenoma composed of two different cell types, one secreting alpha-subunit alone and another cosecreting alpha-subunit and thyrotropin. Terzolo, M., Orlandi, F., Bassetti, M., Medri, G., Paccotti, D., Cortelazzi, D., Angeli, A., Beck-Peccoz, P. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  20. Substitution of the seat-belt region of the thyroid-stimulating hormone (TSH) beta-subunit with the corresponding regions of choriogonadotropin or follitropin confers luteotropic but not follitropic activity to chimeric TSH. Grossmann, M., Szkudlinski, M.W., Wong, R., Dias, J.A., Ji, T.H., Weintraub, B.D. J. Biol. Chem. (1997) [Pubmed]
  21. Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. Jameson, J.L., Klibanski, A., Black, P.M., Zervas, N.T., Lindell, C.M., Hsu, D.W., Ridgway, E.C., Habener, J.F. J. Clin. Invest. (1987) [Pubmed]
  22. Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. Mason, M.E., Friend, K.E., Copper, J., Shupnik, M.A. Biochemistry (1993) [Pubmed]
  23. Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. Ando, S., Sarlis, N.J., Krishnan, J., Feng, X., Refetoff, S., Zhang, M.Q., Oldfield, E.H., Yen, P.M. Mol. Endocrinol. (2001) [Pubmed]
  24. Immunohistochemical studies of human FSH producing pituitary adenomas. Osamura, R.Y., Watanabe, K. Virchows Archiv. A, Pathological anatomy and histopathology. (1988) [Pubmed]
  25. Differentiation behavior of pituitary cells in normal and metamorphosis-arrested larvae of the salamander Hynobius retardatus. Furuta, K., Kanki, K., Wakahara, M. Int. J. Dev. Biol. (2001) [Pubmed]
  26. In vitro effects of mammalian leptin, neuropeptide-Y, beta-endorphin and galanin on transcript levels of thyrotropin beta and common alpha subunit mRNAs in the pituitary of bighead carp (aristichthys nobilis). Chowdhury, I., Chien, J.T., Chatterjee, A., Yu, J.Y. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2004) [Pubmed]
  27. Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas. Friend, K.E., Chiou, Y.K., Laws, E.R., Lopes, M.B., Shupnik, M.A. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  28. Purification and characterization of recombinant human thyrotropin (TSH) isoforms produced by Chinese hamster ovary cells: the role of sialylation and sulfation in TSH bioactivity. Szkudlinski, M.W., Thotakura, N.R., Bucci, I., Joshi, L.R., Tsai, A., East-Palmer, J., Shiloach, J., Weintraub, B.D. Endocrinology (1993) [Pubmed]
  29. Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene. Dacou-Voutetakis, C., Feltquate, D.M., Drakopoulou, M., Kourides, I.A., Dracopoli, N.C. Am. J. Hum. Genet. (1990) [Pubmed]
  30. Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy. Puille, M., Klett, R., Steiner, D., Bauer, R. Nuclear medicine communications. (2005) [Pubmed]
  31. Metabolic clearance and secretion rates of subunits of human thyrotropin. Kourides, I.A., Re, R.N., Weintraub, B.D., Ridgway, E.C., Maloof, F. J. Clin. Invest. (1977) [Pubmed]
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