Genomes and Genes
Gene Symbol: Tshb
Description: thyroid stimulating hormone, beta subunit
Alias: thyrotropin subunit beta, TSH-B, TSH-beta, thyroid-stimulating hormone subunit beta, thyrotropin beta chain
- Gordon D, Woodmansee W, Black J, Dowding J, Bendrick Peart J, Wood W, et al. Domains of Pit-1 required for transcriptional synergy with GATA-2 on the TSH beta gene. Mol Cell Endocrinol. 2002;196:53-66 pubmedPrevious studies showed that Pit-1 functionally cooperates with GATA-2 to stimulate transcription of the TSH beta gene...
- Shibusawa N, Yamada M, Hirato J, Monden T, Satoh T, Mori M. Requirement of thyrotropin-releasing hormone for the postnatal functions of pituitary thyrotrophs: ontogeny study of congenital tertiary hypothyroidism in mice. Mol Endocrinol. 2000;14:137-46 pubmed..Moreover, reflecting its name, TRH has more critical effects on the pituitary thyrotrophs than on other pituitary hormone-producing cells. ..
- Dasen J, O Connell S, Flynn S, Treier M, Gleiberman A, Szeto D, et al. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell. 1999;97:587-98 pubmed
- Treier M, Gleiberman A, O Connell S, Szeto D, McMahon J, McMahon A, et al. Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev. 1998;12:1691-704 pubmed
- Brinkmeier M, Potok M, Davis S, Camper S. TCF4 deficiency expands ventral diencephalon signaling and increases induction of pituitary progenitors. Dev Biol. 2007;311:396-407 pubmed..Thus, TCF4 is necessary both intrinsically and extrinsically to Rathke's pouch to ensure the proper growth of the pituitary gland. ..
- Nikrodhanond A, Ortiga Carvalho T, Shibusawa N, Hashimoto K, Liao X, Refetoff S, et al. Dominant role of thyrotropin-releasing hormone in the hypothalamic-pituitary-thyroid axis. J Biol Chem. 2006;281:5000-7 pubmed..Thus, TRH is absolutely required for both TSH and TH synthesis but is not necessary for thyrotroph cell development. ..
- Pope C, McNeilly J, Coutts S, Millar M, Anderson R, McNeilly A. Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland. Dev Biol. 2006;297:172-81 pubmed..The mechanism(s) responsible for the different molecular regulation of alpha-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation...
- Gordon D, Lewis S, Haugen B, James R, McDermott M, Wood W, et al. Pit-1 and GATA-2 interact and functionally cooperate to activate the thyrotropin beta-subunit promoter. J Biol Chem. 1997;272:24339-47 pubmed..In summary, these data demonstrate functional synergy and physical interaction between homeobox and zinc finger factors and provide insights into the transcriptional mechanisms of thyrotrope-specific gene expression. ..
- Sheng H, Zhadanov A, Mosinger B, Fujii T, Bertuzzi S, Grinberg A, et al. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science. 1996;272:1004-7 pubmed..The determination of all pituitary cell lineages, except the corticotrophs, was affected, suggesting that a distinct, Lhx3-independent ontogenetic pathway exists for the initial specification of this lineage. ..
- Charles M, Suh H, Hjalt T, Drouin J, Camper S, Gage P. PITX genes are required for cell survival and Lhx3 activation. Mol Endocrinol. 2005;19:1893-903 pubmed..Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function. ..
- Ellsworth B, Egashira N, Haller J, Butts D, Cocquet J, Clay C, et al. FOXL2 in the pituitary: molecular, genetic, and developmental analysis. Mol Endocrinol. 2006;20:2796-805 pubmed..These data place FOXL2 in the hierarchy of pituitary developmental control and suggest a role in regulation of Cga gene expression...
- Mortensen A, Schade V, Lamonerie T, Camper S. Deletion of OTX2 in neural ectoderm delays anterior pituitary development. Hum Mol Genet. 2015;24:939-53 pubmed publisher..Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. ..
- Kerscher S, Church R, Boyd Y, Lyon M. Mapping of four mouse genes encoding eye lens-specific structural, gap junction, and integral membrane proteins: Cryba1 (crystallin beta A3/A1), Crybb2 (crystallin beta B2), Gja8 (MP70), and Lim2 (MP19). Genomics. 1995;29:445-50 pubmed..5 +/- 2.5 cM proximal to Ngfg. All four map positions, when compared with the corresponding positions in human, lie within known regions of conserved synteny between mouse and human chromosomes. ..
- Kim K, Park K, Song S, Kim K. Insulin represses transcription of the thyroid stimulating hormone beta-subunit gene through increased recruitment of nuclear factor I. J Biol Chem. 2010;285:32003-11 pubmed publisher..Taken together, this study provides new insights of the delicate regulations of energy metabolism and hormonal homeostasis. ..
- Kioussi C, Briata P, Baek S, Rose D, Hamblet N, Herman T, et al. Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. 2002;111:673-85 pubmed
- Li Y, Lacerda D, Warman M, Beier D, Yoshioka H, Ninomiya Y, et al. A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis. Cell. 1995;80:423-30 pubmed..The results also suggest that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix. ..
- Bassett J, Williams A, Murphy E, Boyde A, Howell P, Swinhoe R, et al. A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism. Mol Endocrinol. 2008;22:501-12 pubmed..Furthermore, TSH did not affect the differentiation or function of osteoblasts or osteoclasts in vitro. These data indicate the hypothalamic-pituitary-thyroid axis regulates skeletal development via the actions of T(3). ..
- Kanki K, Wakahara M. Spatio-temporal expression of TSH beta and FSH beta genes in normally metamorphosing, metamorphosed, and metamorphosis-arrested Hynobius retardatus. Gen Comp Endocrinol. 2000;119:276-86 pubmedExpression patterns of TSH beta and FSH beta genes were investigated in normally metamorphosing and metamorphosed individuals and in goitrogen-treated (TU-SPC), metamorphosis-arrested larvae of a Japanese salamander, Hynobius retardatus, ..
- Liu J, Lin C, Gleiberman A, Ohgi K, Herman T, Huang H, et al. Tbx19, a tissue-selective regulator of POMC gene expression. Proc Natl Acad Sci U S A. 2001;98:8674-9 pubmed..It is suggested that Tbx19, depending on the presence of synergizing transcription factors, can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters. ..
- Davis S, Mortensen A, Camper S. Birthdating studies reshape models for pituitary gland cell specification. Dev Biol. 2011;352:215-27 pubmed publisher..We propose that signals intrinsic to Rathke's pouch are necessary for cell specification between e11.5 and e13.5 and that cell-cell communication likely plays an important role in regulating this process...
- Dasen J, Martinez Barbera J, Herman T, Connell S, Olson L, Ju B, et al. Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev. 2001;15:3193-207 pubmed
- Stefaneanu L, Powell Braxton L, Won W, Chandrashekar V, Bartke A. Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene. Endocrinology. 1999;140:3881-9 pubmed..In conclusion, IGF-I plays no role in differentiation of pituitary cells, affects the size of somatotrophs in females, and is a stimulator of lactotrophs in both genders. ..
- Bentley C, Zidehsarai M, Grindley J, Parlow A, Barth Hall S, Roberts V. Pax6 is implicated in murine pituitary endocrine function. Endocrine. 1999;10:171-7 pubmed
- Repetto E, Briata P, Kuziner N, Harfe B, McManus M, Gherzi R, et al. Let-7b/c enhance the stability of a tissue-specific mRNA during mammalian organogenesis as part of a feedback loop involving KSRP. PLoS Genet. 2012;8:e1002823 pubmed publisher..Our study unveils a functional crosstalk between miRNA- and AMD-dependent gene regulation during mammalian organogenesis events. ..
- Wolf O, Kourides I, Gurr J. Expression of the gene for the beta subunit of mouse thyrotropin results in multiple mRNAs differing in their 5'-untranslated regions. J Biol Chem. 1987;262:16596-603 pubmedThe gene encoding the beta subunit of mouse thyrotropin (TSH beta) has been isolated from a mouse genomic library, and its nucleotide sequence has been determined...
- Castinetti F, Brinkmeier M, Mortensen A, Vella K, Gergics P, Brue T, et al. ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism. Mol Endocrinol. 2015;29:1510-21 pubmed publisher..Thyrotrope-specific disruption of Isl1 with Tshb-cre is permissive for normal serum TSH, but T4 levels are decreased, suggesting decreased thyrotrope function...
- Oakey R, Howard T, Hogarth P, Tani K, Seldin M. Chromosomal mapping of the high affinity Fc gamma receptor gene. Immunogenetics. 1992;35:279-82 pubmed
- Varghese S, Montufar Solis D, Vincent B, Klein J. Virus infection activates thyroid stimulating hormone synthesis in intestinal epithelial cells. J Cell Biochem. 2008;105:271-6 pubmed publisher..These findings have direct functional implications for understanding a TSH immune-endocrine circuit in the small intestine. ..
- Cao D, Ma X, Cai J, Luan J, Liu A, Yang R, et al. ZBTB20 is required for anterior pituitary development and lactotrope specification. Nat Commun. 2016;7:11121 pubmed publisher..In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification. ..
- Raetzman L, Cai J, Camper S. Hes1 is required for pituitary growth and melanotrope specification. Dev Biol. 2007;304:455-66 pubmed..These results demonstrate that Notch signaling plays multiple roles in pituitary development, influencing precursor number, organ size, cell differentiation and ultimately cell fate. ..
- Wilson D, Wyatt D. Immunocytochemistry of ambiguous cells in adult and embryonic dwarf (dw) mouse pituitaries. Anat Rec. 1993;236:671-8 pubmed..The results thus suggest that adult dwarf pituitaries may retain an embryonic or incompletely differentiated form of ACTH cells. ..
- Vesper A, Raetzman L, Camper S. Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty. Endocrinology. 2006;147:1654-63 pubmed..We hypothesize that variation in PROP1 expression could affect the growth spurt and the onset of puberty in humans...
- Foreman J, Blizard D, Gerhard G, Mack H, Lang D, Van Nimwegen K, et al. Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice. Physiol Genomics. 2005;23:295-303 pubmed
- Zhang F, Tanasa B, Merkurjev D, Lin C, Song X, Li W, et al. Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program. Proc Natl Acad Sci U S A. 2015;112:1380-5 pubmed publisher..These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type. ..
- Sun Y, Bak B, Schoenmakers N, van Trotsenburg A, Oostdijk W, Voshol P, et al. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nat Genet. 2012;44:1375-81 pubmed publisher..Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. ..
- Moran T, Goldberg L, Serviss S, Raetzman L. Numb deletion in POMC-expressing cells impairs pituitary intermediate lobe cell adhesion, progenitor cell localization, and neuro-intermediate lobe boundary formation. Mol Endocrinol. 2011;25:117-27 pubmed publisher..Unexpectedly, Notch activity appears normal in conditional knockout mice. Thus, Numb is critical for maintaining cell-cell interactions in the pituitary intermediate lobe that are essential for proper cell placement. ..
- Kingsmore S, Moseley W, Watson M, Sabina R, Holmes E, Seldin M. Long-range restriction site mapping of a syntenic segment conserved between human chromosome 1 and mouse chromosome 3. Genomics. 1990;7:75-83 pubmed..Moreover, the data suggest profound conservation of genomic organization during mammalian evolution. ..
- Kita A, Imayoshi I, Hojo M, Kitagawa M, Kokubu H, Ohsawa R, et al. Hes1 and Hes5 control the progenitor pool, intermediate lobe specification, and posterior lobe formation in the pituitary development. Mol Endocrinol. 2007;21:1458-66 pubmed..Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis. ..
- Pajukanta P, Bodnar J, Sallinen R, Chu M, Airaksinen T, Xiao Q, et al. Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL. Mamm Genome. 2001;12:238-45 pubmed..Further studies identifying and sequencing the Hyplip1 gene will show whether the same gene predisposes to hyperlipidemia in human and mouse. ..
- Okada R, Iwata T, Kato T, Kikuchi M, Yamamoto K, Kikuyama S. Cloning of bullfrog thyroid-stimulating hormone (TSH) beta subunit cDNA: expression of TSHbeta mRNA during metamorphosis. Gen Comp Endocrinol. 2000;119:224-31 pubmed..The deduced amino acid sequence showed 40-61% homologies with the sequences of TSH beta subunits of other vertebrates...
- Sheng H, Moriyama K, Yamashita T, Li H, Potter S, Mahon K, et al. Multistep control of pituitary organogenesis. Science. 1997;278:1809-12 pubmed..Thus, Lhx3 and Lhx4 dictate pituitary organ identity by controlling developmental decisions at multiple stages of organogenesis. ..
- Broad T, Burkin D, Cambridge L, Carpenter M, Jones C. Four loci from human chromosome 1 are physically assigned to sheep chromosome 1p. Mamm Genome. 1995;6:551-3 pubmed
- Metz H, Wray S. Use of mutant mouse lines to investigate origin of gonadotropin-releasing hormone-1 neurons: lineage independent of the adenohypophysis. Endocrinology. 2010;151:766-73 pubmed publisher..These results indicate that in mice, GnRH-1 cells develop independent of the adenohypophyseal placode and are associated early with the formation of the nasal placode. ..
- Sajedi E, Gaston Massuet C, Signore M, Andoniadou C, Kelberman D, Castro S, et al. Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. Dis Model Mech. 2008;1:241-54 pubmed publisher..Together, these results suggest that the I26T mutation yields a hypomorphic allele, whereas R160C produces a null allele and, consequently, a more severe phenotype in both mice and humans...
- Cha K, Douglas K, Potok M, Liang H, Jones S, Camper S. WNT5A signaling affects pituitary gland shape. Mech Dev. 2004;121:183-94 pubmed..This study suggests that the primary role of Wnt5a in the developing pituitary gland is in establishment of the shape of the gland. ..
- Weiss R, Forrest D, Pohlenz J, Cua K, Curran T, Refetoff S. Thyrotropin regulation by thyroid hormone in thyroid hormone receptor beta-deficient mice. Endocrinology. 1997;138:3624-9 pubmed..However, although TR alpha alone can mediate thyroid hormone induced TSH suppression, TR beta enhances the sensitivity of TSH down-regulation and may be essential for the complete suppression of TSH. ..
- Bosse R, Fumagalli F, Jaber M, Giros B, Gainetdinov R, Wetsel W, et al. Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter. Neuron. 1997;19:127-38 pubmed..These results reveal an unexpected and important role or DA in the control of developmental events in the pituitary gland and assign a critical role for hypothalamic DA reuptake in regulating these events. ..
- Moseley W, Seldin M. Definition of mouse chromosome 1 and 3 gene linkage groups that are conserved on human chromosome 1: evidence that a conserved linkage group spans the centromere of human chromosome 1. Genomics. 1989;5:899-905 pubmed..These studies provide a model for examination of specific evolutionary events. ..
- Cheung L, Okano H, Camper S. Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes. Mol Cell Endocrinol. 2017;439:213-223 pubmed publisher..In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. ..
- Wood W, Gordon D, Ridgway E. Expression of the beta-subunit gene of murine thyrotropin results in multiple messenger ribonucleic acid species which are generated by alternative exon splicing. Mol Endocrinol. 1987;1:875-83 pubmedThe current studies reveal that expression of the mouse TSH beta-subunit gene in the pituitary gland and TtT97 murine thyrotropic tumor results in multiple mRNAs which arise by alternative splicing...
- Raetzman L, Ward R, Camper S. Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Development. 2002;129:4229-39 pubmed..Thus, Lhx4 and Prop1 have critical, but mechanistically different roles in specification and expansion of specialized anterior pituitary cells. ..
- Goldsmith S, Lovell Badge R, Rizzoti K. SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary. Development. 2016;143:2376-88 pubmed publisher..Therefore, SOX2 has two independent roles during pituitary morphogenesis; firstly, promotion of progenitor proliferation, and subsequently, acquisition of melanotroph identity. ..