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Tshr  -  thyroid stimulating hormone receptor

Mus musculus

Synonyms: AI481368, TSH-R, Thyroid-stimulating hormone receptor, Thyrotropin receptor, hypothroid, ...
 
 
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Disease relevance of Tshr

  • These findings, including recruitment-like behavior and the restoration of response magnitude at high levels but not low, suggest that the cochlear amplifier is the primary locus of an enduring otological defect associated with hypothyroidism in the Tshr mouse [1].
  • Graves' disease involves a breakdown in self-tolerance to the TSH receptor (TSHR) [2].
  • Immunization with adenovirus encoding the TSH receptor (TSHR) or its A-subunit induces Graves' hyperthyroidism in BALB/c and BALB/c x C57BL/6 offspring but not C57BL/6 mice [3].
  • CXB strains were studied before and after A-subunit adenovirus immunization for TSHR antibodies (TBI, inhibition of TSH binding), serum T4, and thyroid histology [3].
  • Histological and ultrastructural abnormalities in the gland were similar to those seen in certain cases of human congenital hypothyroidism with TSH receptor insensitivity of the thyroid gland [4].
 

Psychiatry related information on Tshr

  • Abnormal neuroanatomical development in selected brain regions may be the factor underlying the abnormalities in reflexive, locomotor, and adaptive behavior seen in the hyt/hyt mouse and other hypothyroid animals [5].
  • Mutant (hyt/hyt) mice exhibited a distinctive pattern of sensory pathology that was characterized by their insensitivity to sound, prolonged response latencies, reduced peak amplitudes, and steep latency-intensity curves relative to the phenotypically normal, euthyroid, +/hyt littermates [1].
  • The effects of congenital hypothyroidism using the hyt/hyt mouse on locomotor activity and learned behavior [6].
 

High impact information on Tshr

 

Chemical compound and disease context of Tshr

  • The otological consequences of hypothyroidism and the outcome of thyroxin (T4) administration during the developmental period preceding the onset of hearing were examined in mice that express a point mutation in the gene encoding the thyrotropin receptor (Tshr), the so-called hyt mouse [1].
  • The body weight, the weight of different brain regions, and the plasma thyroxine and triiodothyronine levels of hyt/hyt mice were significantly lower than those of the age-matched hyt/+ controls [11].
  • To overcome the handicap of very low TSHR expression in thyroid cells, we generated a TSHR-expressing adenovirus (TSHR-Ad-RGD) with an integrin-binding RGD motif enabling efficient entry into cells lacking the coxsackie-adenovirus receptor [12].
  • The hyt/hyt mouse has a severe and pervasive primary inherited hypothyroidism with significantly depressed serum T4, elevated serum and pituitary TSH, and reduced thyroid gland iodide uptake [13].
 

Biological context of Tshr

 

Anatomical context of Tshr

  • Moreover, T cells from both strains recognized the same two epitopes from a panel of 29 synthetic peptides encompassing the TSHR ectodomain and extracellular loops [2].
  • These findings demonstrate that TSH/cAMP regulates TSHR mRNA levels in adipocytes via a regulatory system distinct from that used in FRTL-5 cells [16].
  • Nuclear run-on assays show that the ability of TSH/cAMP to decrease TSHR mRNA levels in 3T3-L1 cells reflects transcriptional regulation [16].
  • Western blot analyses demonstrated that the mutant and wild-type receptors were processed through a similar series of precursors and that a mature 95-kilodalton form of the mutant TSH-R was produced, consistent with its insertion into the plasma membrane [17].
  • We previously have demonstrated that rat adipose tissue expresses TSH receptor (TSHR) messenger RNAs (mRNAs) at levels approaching those detected in the thyroid [16].
 

Associations of Tshr with chemical compounds

  • We conclude that auditory function is impaired in hypothyroid Tshr animals throughout development and that impairment is profound when individuals are not exposed to maternal thyroid hormone, i.e., a clear thyroxin-dependent critical prenatal period exists in the Tshr mutant mouse [14].
  • These results suggest interactions between the extracellular and transmembrane domains of the TSH-R and indicate that this highly conserved proline is required for normal receptor structure and function [17].
  • It is also shown that while congenital hypothyroid hyt/hyt male mice, exposed to maternal T3 in the gestational period, exhibit diminished but existent androgen-dependent cortical responses, mice exposed to goitrogens during gestation and postnatally are unable to express the gene even at postnatal day ninety [18].
  • Replacement of thyroxin during the first 10 postnatal days in hyt/hyt(h) pups had little to no effect on the development of auditory function, although more animals from this group were responsive at very high stimulation levels [14].
  • When T4 was administered to hyt/hyt animals, pinna-raising occurred earlier than in untreated animals [1].
 

Physical interactions of Tshr

  • 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 [19].
 

Regulatory relationships of Tshr

  • 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 [20].
 

Other interactions of Tshr

 

Analytical, diagnostic and therapeutic context of Tshr

References

  1. Consequences of hypothyroidism on auditory system function in Tshr mutant (hyt) mice. Sprenkle, P.M., McGee, J., Bertoni, J.M., Walsh, E.J. J. Assoc. Res. Otolaryngol. (2001) [Pubmed]
  2. Thyrotropin receptor knockout mice: studies on immunological tolerance to a major thyroid autoantigen. Pichurin, P.N., Pichurina, O., Marians, R.C., Chen, C.R., Davies, T.F., Rapoport, B., McLachlan, S.M. Endocrinology (2004) [Pubmed]
  3. 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]
  4. Evaluation and characterization of the hyt/hyt hypothyroid mouse. II. Abnormalities of TSH and the thyroid gland. Stein, S.A., Shanklin, D.R., Krulich, L., Roth, M.G., Chubb, C.M., Adams, P.M. Neuroendocrinology (1989) [Pubmed]
  5. Biology of the congenitally hypothyroid hyt/hyt mouse. Biesiada, E., Adams, P.M., Shanklin, D.R., Bloom, G.S., Stein, S.A. Adv. Neuroimmunol. (1996) [Pubmed]
  6. The effects of congenital hypothyroidism using the hyt/hyt mouse on locomotor activity and learned behavior. Anthony, A., Adams, P.M., Stein, S.A. Hormones and behavior. (1993) [Pubmed]
  7. TSH is a negative regulator of skeletal remodeling. Abe, E., Marians, R.C., Yu, W., Wu, X.B., Ando, T., Li, Y., Iqbal, J., Eldeiry, L., Rajendren, G., Blair, H.C., Davies, T.F., Zaidi, M. Cell (2003) [Pubmed]
  8. Local hormone networks and intestinal T cell homeostasis. Wang, J., Whetsell, M., Klein, J.R. Science (1997) [Pubmed]
  9. Inherited primary hypothyroidism in mice. Beamer, W.J., Eicher, E.M., Maltais, L.J., Southard, J.L. Science (1981) [Pubmed]
  10. Concentration-dependent regulation of thyrotropin receptor function by thyroid-stimulating antibody. Ando, T., Latif, R., Davies, T.F. J. Clin. Invest. (2004) [Pubmed]
  11. Subcellular distribution of carbonic anhydrase and Na+,K(+)-ATPase in the brain of the hyt/hyt hypothyroid mice. Li, J., Chow, S.Y. Neurochem. Res. (1994) [Pubmed]
  12. Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface. Chen, C.R., Chazenbalk, G.D., Wawrowsky, K.A., McLachlan, S.M., Rapoport, B. Endocrinology (2006) [Pubmed]
  13. The site of the molecular defect in the thyroid gland of the hyt/hyt mouse: abnormalities in the TSH receptor-G protein complex. Stein, S.A., Zakarija, M., McKenzie, J.M., Shanklin, D.R., Palnitkar, M.B., Adams, P.M. Thyroid (1991) [Pubmed]
  14. Development of auditory brainstem responses (ABRs) in Tshr mutant mice derived from euthyroid and hypothyroid dams. Sprenkle, P.M., McGee, J., Bertoni, J.M., Walsh, E.J. J. Assoc. Res. Otolaryngol. (2001) [Pubmed]
  15. Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice. Marians, R.C., Ng, L., Blair, H.C., Unger, P., Graves, P.N., Davies, T.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Regulation of thyrotropin receptor gene expression in 3T3-L1 adipose cells is distinct from its regulation in FRTL-5 thyroid cells. Shimura, H., Haraguchi, K., Endo, T., Onaya, T. Endocrinology (1997) [Pubmed]
  17. The thyrotropin (TSH) receptor transmembrane domain mutation (Pro556-Leu) in the hypothyroid hyt/hyt mouse results in plasma membrane targeting but defective TSH binding. Gu, W.X., Du, G.G., Kopp, P., Rentoumis, A., Albanese, C., Kohn, L.D., Madison, L.D., Jameson, J.L. Endocrinology (1995) [Pubmed]
  18. Effects of thyroid hormone on the androgenic expression of KAP gene in mouse kidney. Solé, E., Calvo, R., Obregón, M.J., Meseguer, A. Mol. Cell. Endocrinol. (1996) [Pubmed]
  19. 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]
  20. 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]
  21. 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]
  22. A dominant negative CREB (cAMP response element-binding protein) isoform inhibits thyrocyte growth, thyroid-specific gene expression, differentiation, and function. Nguyen, L.Q., Kopp, P., Martinson, F., Stanfield, K., Roth, S.I., Jameson, J.L. Mol. Endocrinol. (2000) [Pubmed]
  23. 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]
 
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