{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:23:34Z","timestamp":1788384214217,"version":"build-2803163510"},"reference-count":44,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The expression of receptor protein tyrosine phosphatase sigma (PTP\u03c3) is developmentally regulated in neuronal and neuroendocrine tissues. We have previously shown that mice deficient in PTP\u03c3 demonstrate nervous system abnormalities, pituitary hypoplasia, increased neonatal mortality (60%), and death from a wasting syndrome at 2\u20133 wk of age (38%). We have now examined the role of PTP\u03c3 on pituitary, pancreas and enteroendocrine cytodifferentiation, hormone production, and development. The adenohypophyses of PTP\u03c3(\u2212\/\u2212) mice were small and exhibited reduced GH and PRL immunoreactivity. Cells containing TSH, LH, FSH, ACTH, pituitary-specific POU homeodomain factor (Pit-1), ER, and steroidogenic factor 1 were found in normal proportions and distributions. The diminished expression of GH and PRL was not associated with apoptosis of somatotrophs or lactotrophs. Pit-1-positive TSH-negative cells were detected, suggesting that impaired GH and PRL synthesis was not attributable to Pit-1 deficiency. In the knockout mice, pancreatic islets were hypoplastic with reduced insulin immunoreactivity, and there was also variable expression of gut hormones. Functionally, the GH deficiency was associated with hypoglycemia and death in the PTP\u03c3(\u2212\/\u2212) neonate and accordingly, ip administration of GH rescued the PTP\u03c3(\u2212\/\u2212) neonate and normalized the blood glucose. These data indicate that PTP\u03c3 plays a major role in differentiation and development of the neuroendocrine system.<\/jats:p>","DOI":"10.1210\/mend.16.1.0756","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:31:13Z","timestamp":1389202273000},"page":"155-169","source":"Crossref","is-referenced-by-count":19,"title":["Pituitary, Pancreatic and Gut Neuroendocrine Defects in Protein Tyrosine Phosphatase- Sigma-Deficient Mice"],"prefix":"10.1210","volume":"16","author":[{"given":"Jane","family":"Batt","sequence":"first","affiliation":[{"name":"The Hospital for Sick Children (J.B., C.F., D.R.), Program in Cell Biology, and Institute of Medical Science and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Asa","sequence":"additional","affiliation":[{"name":"Departments of Pathology (S.A.), University of Toronto and Laboratory Medicine and Pathobiology, University Health Network, Toronto, Ontario, Canada, M5G 2C4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Fladd","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children (J.B., C.F., D.R.), Program in Cell Biology, and Institute of Medical Science and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rotin","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children (J.B., C.F., D.R.), Program in Cell Biology, and Institute of Medical Science and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614155643700_R1","doi-asserted-by":"crossref","first-page":"24880","DOI":"10.1016\/S0021-9258(19)74547-5","article-title":"A novel receptor tyrosine phosphatase \u03c3 that is highly expressed in the nervous system.","volume":"268","author":"Yan","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071614155643700_R2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1042\/bj3020039","article-title":"Molecular cloning and expression of a unique receptor-like protein tyrosine phosphatase in the leukocyte common-antigen-related phosphatase family.","volume":"302","author":"Zhang","year":"1994","journal-title":"Biochem J"},{"key":"2020071614155643700_R3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0896-6273(00)81091-0","article-title":"The tyrosine Kinase Abl and its substrate enabled collaborate with the receptor phosphatase Dlar to control motor axon guidance.","volume":"22","author":"Wills","year":"1999","journal-title":"Neuron"},{"key":"2020071614155643700_R4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0092-8674(00)81036-3","article-title":"The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila.","volume":"84","author":"Krueger","year":"1996","journal-title":"Cell"},{"key":"2020071614155643700_R5","doi-asserted-by":"crossref","first-page":"4968","DOI":"10.1523\/JNEUROSCI.13-11-04968.1993","article-title":"Protein tyrosine phosphatases expressed in the developing rat brain.","volume":"13","author":"Sahin","year":"1993","journal-title":"J Neurosci"},{"key":"2020071614155643700_R6","first-page":"566","article-title":"Expression of LAR-PTP2 in rat lung is confined to proliferating epithelia lining the airways and airsacs.","volume":"14","author":"Kim","year":"1996","journal-title":"Am J Physiol"},{"key":"2020071614155643700_R7","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/cne.903510410","article-title":"Seven protein tyrosine phosphatases are differentially expressed in the developing rat brain","volume":"351","author":"Sahin","year":"1995","journal-title":"J Comp Neurol"},{"key":"2020071614155643700_R8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0925-4773(98)00119-1","article-title":"Developmental expression of the cell adhesion molecule-like protein tyrosine phosphatases LAR, RPTP\u03b4 and RPTP\u03c3 in the mouse.","volume":"77","author":"Schaapveld","year":"1998","journal-title":"Mech Dev"},{"key":"2020071614155643700_R9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/jnr.490410303","article-title":"Expression of receptor protein tyrosine phosphatase-\u03c3 (RPTP-\u03c3) in the nervous system of the developing and adult rat.","volume":"41","author":"Wang","year":"1995","journal-title":"J Neurosci Res"},{"key":"2020071614155643700_R10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/6866","article-title":"Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor tyrosine phosphatase PTP\u03c3.","volume":"21","author":"Wallace","year":"1999","journal-title":"Nat Genet"},{"key":"2020071614155643700_R11","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/6859","article-title":"Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase\u03c3.","volume":"21","author":"Elchebly","year":"1999","journal-title":"Nat Genet"},{"key":"2020071614155643700_R12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1023\/A:1009948813587","article-title":"Molecular determinants of pituitary cytodifferentiation.","volume":"1","author":"Asa","year":"1999","journal-title":"Pituitary"},{"key":"2020071614155643700_R13","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/339538a0","article-title":"Transgenic mice with inducible dwarfism.","volume":"339","author":"Borrelli","year":"1989","journal-title":"Nature"},{"key":"2020071614155643700_R14","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/347528a0","article-title":"Dwarf locus mutants lacking three pituitary cell types result from mutation in the POU-domain gene Pit-1.","volume":"347","author":"Li.","year":"1990","journal-title":"Nature"},{"key":"2020071614155643700_R15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/(SICI)1097-0029(19971015)39:2<98::AID-JEMT2>3.0.CO;2-S","article-title":"Development and differentiation of pituitary cells.","volume":"39","author":"Dubois","year":"1997","journal-title":"Microsc Res Tech"},{"key":"2020071614155643700_R16","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1101\/gad.12.11.1691","article-title":"Multistep signaling requirements for pituitary organogenesis in vivo.","volume":"12","author":"Treier","year":"1998","journal-title":"Genes Dev"},{"key":"2020071614155643700_R17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1385\/ENDO:12:2:99","article-title":"Genetic regulation of the embryology of the pituitary gland and somatotrophs.","volume":"12","author":"Cohen","year":"2000","journal-title":"Endocrine"},{"key":"2020071614155643700_R18","first-page":"1","article-title":"Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo.","volume":"55","author":"Rosenfeld","year":"2000","journal-title":"Recent Prog Horm Res"},{"key":"2020071614155643700_R19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1210\/edrv-11-1-177","article-title":"Molecular biology of the pituitary gonadotrophs","volume":"11","author":"Gharib","year":"1990","journal-title":"Endocr Rev"},{"key":"2020071614155643700_R20","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1101\/gad.8.19.2302","article-title":"The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.","volume":"8","author":"Ingraham","year":"1994","journal-title":"Genes Dev"},{"key":"2020071614155643700_R21","doi-asserted-by":"crossref","first-page":"6673","DOI":"10.1128\/MCB.17.11.6673","article-title":"NeuroD1\/\u03b2 2 contributes to cell specific transcription of the pro-opiomelanocortin gene.","volume":"17","author":"Poulin","year":"1997","journal-title":"Mol Cell Biol"},{"key":"2020071614155643700_R22","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1128\/MCB.13.4.2342","article-title":"Cell-specific helix-loop-helix factor required for pituitary expression of the pro- opiomelanocortin gene.","volume":"13","author":"Therrien","year":"1993","journal-title":"Mol Cell Biol"},{"key":"2020071614155643700_R23","first-page":"694","article-title":"Synergistic interactions between Pit-1 and other elements are required for effective somatotroph rat growth hormone gene expression in transgenic mice.","volume":"7","author":"Lira","year":"1993","journal-title":"Mol Endocrinol"},{"key":"2020071614155643700_R24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0739-7240(95)00059-3","article-title":"Control of growth hormone synthesis.","volume":"13","author":"Tuggle","year":"1996","journal-title":"Domest Anim Endocrinol"},{"key":"2020071614155643700_R25","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1101\/gad.7.9.1674","article-title":"Identification of a novel zinc finger protein binding a conserved element critical for Pit-1 dependent growth hormone gene expression.","volume":"7","author":"Lipkin","year":"1993","journal-title":"Genes Dev"},{"key":"2020071614155643700_R26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0303-7207(99)00200-2","article-title":"Mouse growth hormone transcription factor Zn-16: unique bipartite structure containing tandemly repeated zinc finger domains not reported in rat Zn-15.","volume":"159","author":"VanderHeyden","year":"2000","journal-title":"Mol Cell Endocrinol"},{"key":"2020071614155643700_R27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000127177","article-title":"Pituitary morphology in human anencephalic fetuses.","volume":"65","author":"Pilavdzic","year":"1997","journal-title":"Neuroendocrinology"},{"key":"2020071614155643700_R28","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)80770-9","article-title":"Reciprocal interactions of Pit 1 and GATA 2 mediate signaling gradient-induced determination of pituitary cell types.","volume":"97","author":"Dasen","year":"1999","journal-title":"Cell"},{"key":"2020071614155643700_R29","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0955-0674(99)00034-4","article-title":"Signaling mechanisms in pituitary morphogenesis and cell fate determination.","volume":"11","author":"Dasen","year":"1999","journal-title":"Curr Opin Cell Biol"},{"key":"2020071614155643700_R30","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1210\/mend-4-12-1964","article-title":"Both Pit-1 and the estrogen receptor are required for the estrogen responsiveness of the rat prolactin gene.","volume":"4","author":"Day","year":"1990","journal-title":"Mol Endocrinol"},{"key":"2020071614155643700_R31","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1128\/MCB.15.5.2849","article-title":"Functional interaction of C-Ets-1 and GHF-1\/Pit-1 mediates Ras activation of pituitary-specific gene expression: mapping of the essential c-Ets-1 domain.","volume":"15","author":"Bradford","year":"1995","journal-title":"Mol Cell Biol"},{"key":"2020071614155643700_R32","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1074\/jbc.275.5.3100","article-title":"The Pit-1 homeodomain and \u03b2-domain interact with Ets-1 and modulate synergistic activation of the rat prolactin promoter.","volume":"275","author":"Bradford","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071614155643700_R33","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1056\/NEJM199904153401510","article-title":"The causes of neonatal hypoglycemia.","volume":"340","author":"Stanley","year":"1999","journal-title":"N Engl J Med"},{"key":"2020071614155643700_R34","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0","article-title":"On the development of the islets of Langerhans.","volume":"43","author":"Larsson","year":"1998","journal-title":"Microsc Res Tech"},{"key":"2020071614155643700_R35","first-page":"247","article-title":"Development of pancreatic islets.","volume":"3","author":"Yamaoka","year":"1999","journal-title":"Int J Mol Med"},{"key":"2020071614155643700_R36","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2337\/diab.45.9.1223","article-title":"Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact.","volume":"45","author":"Beattie","year":"1996","journal-title":"Diabetes"},{"key":"2020071614155643700_R37","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1210\/endo.132.2.8425500","article-title":"Effect of homologous placental lactogens, prolactins, and growth hormones on islet \u03b2 cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of human islet function during pregnancy.","volume":"132","author":"Brelje","year":"1993","journal-title":"Endocrinology"},{"key":"2020071614155643700_R38","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.2337\/diab.44.12.1458","article-title":"Growth factor\/matrix-induced proliferation of human adult \u03b2 cells.","volume":"44","author":"Hayek","year":"1995","journal-title":"Diabetes"},{"key":"2020071614155643700_R39","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1210\/endo-110-2-600","article-title":"Effects of growth hormone, prolactin, and placental lactogens on insulin content and release, and deoxyribonucleic acid synthesis in cultured pancreatic islets.","volume":"110","author":"Nielsen","year":"1982","journal-title":"Endocrinology"},{"key":"2020071614155643700_R40","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s001090050302","article-title":"\u03b2 Cell proliferation and growth factors.","volume":"77","author":"Nielsen","year":"1999","journal-title":"J Mol Med"},{"key":"2020071614155643700_R41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2337\/diab.32.1.67","article-title":"Effect of MtTW15 mammosomatotrophic tumours on pancreatic islet hormones.","volume":"32","author":"Parsons","year":"1983","journal-title":"Diabetes"},{"key":"2020071614155643700_R42","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/0955-0674(94)90047-7","article-title":"Differentiation and self-renewal in the mouse gastrointestinal epithelium.","volume":"6","author":"Gordon","year":"1994","journal-title":"Curr Opin Cell Biol"},{"key":"2020071614155643700_R43","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1749-6632.1998.tb11120.x","article-title":"Molecular mechanisms of enteroendocrine differentiation.","volume":"859","author":"Hocker","year":"1998","journal-title":"Ann NY Acad Sci"},{"key":"2020071614155643700_R44","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1016\/S0021-9258(19)67690-8","article-title":"Expression of liver fatty acid-binding protein\/human growth hormone fusion genes within the enterocyte and enteroendocrine cell populations of fetal transgenic mice.","volume":"266","author":"Roth","year":"1991","journal-title":"J Biol Chem"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/16\/1\/155\/8961110\/mend0155.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/16\/1\/155\/8961110\/mend0155.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:30:35Z","timestamp":1647909035000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/16\/1\/155\/2741446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/mend.16.1.0756","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1,1]]}}}