{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:13:23Z","timestamp":1790054003233,"version":"4.0.1"},"reference-count":42,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT\/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1\/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R\u2212\/\u2212 mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.<\/jats:p>","DOI":"10.1210\/me.2013-1008","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T03:30:36Z","timestamp":1366687836000},"page":"953-965","source":"Crossref","is-referenced-by-count":34,"title":["Each Individual Isoform of the Dopamine D2 Receptor Protects from Lactotroph Hyperplasia"],"prefix":"10.1210","volume":"27","author":[{"given":"Daniela","family":"Radl","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM\/UCI U904, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California 92617"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"De Mei","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM\/UCI U904, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California 92617"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM\/UCI U904, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California 92617"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM\/UCI U904, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California 92617"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM\/UCI U904, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California 92617"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614140175000_B1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1210\/edrv.22.6.0451","article-title":"Dopamine as a prolactin (PRL) inhibitor","volume":"22","author":"Ben-Jonathan","year":"2001","journal-title":"Endocr Rev"},{"key":"2020071614140175000_B2","doi-asserted-by":"crossref","first-page":"e18097","DOI":"10.1371\/journal.pone.0018097","article-title":"Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 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A key step in the transcriptional suppression of the prolactin gene","volume":"277","author":"Liu","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071614140175000_B41","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1095\/biolreprod62.6.1486","article-title":"Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells","volume":"62","author":"Kanasaki","year":"2000","journal-title":"Biol Reprod"},{"key":"2020071614140175000_B42","first-page":"614","article-title":"Analysis of the role of the mitogen-activated protein kinase in mediating cyclic-adenosine 3\u2032,5\u2032-monophosphate effects on prolactin promoter activity","volume":"15","author":"Kievit","year":"2001","journal-title":"Mol Endocrinol"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/27\/6\/953\/8939052\/mend0953.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/27\/6\/953\/8939052\/mend0953.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T11:59:58Z","timestamp":1644839998000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/27\/6\/953\/2615139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,1]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2013-1008","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,1]]}}}