{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:11:19Z","timestamp":1791216679550,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD059056"],"award-info":[{"award-number":["R01HD059056"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD093461"],"award-info":[{"award-number":["R01HD093461"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD087057"],"award-info":[{"award-number":["R01HD087057"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM103425"],"award-info":[{"award-number":["P20 GM103425"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM11070"],"award-info":[{"award-number":["P30GM11070"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK113776\u201001"],"award-info":[{"award-number":["1R01DK113776\u201001"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In normal individuals, pituitary somatotrophs optimise body composition by responding to metabolic signals from leptin. To identify mechanisms behind the regulation of somatotrophs by leptin, we used Cre\u2010LoxP technology to delete leptin receptors (LEPR) selectively in somatotrophs and developed populations purified by fluorescence\u2010activated cell sorting (FACS) that contained 99% somatotrophs. FACS\u2010purified,\n                    <jats:italic>Lepr<\/jats:italic>\n                    \u2010null somatotrophs showed reduced levels of growth hormone (GH), growth hormone\u2010releasing hormone receptor (GHRHR), and Pou1f1 proteins and\n                    <jats:italic>Gh (<\/jats:italic>\n                    females\n                    <jats:italic>)<\/jats:italic>\n                    and\n                    <jats:italic>Ghrhr<\/jats:italic>\n                    (both sexes) mRNAs. Pure somatotrophs also expressed thyroid\u2010stimulating hormone (TSH) and prolactin (PRL), both of which were reduced in pure somatotrophs lacking LEPR. This introduced five gene products that were targets of leptin. In the present study, we tested the hypothesis that leptin is both a transcriptional and a post\u2010transcriptional regulator of these gene products. Our tests showed that Pou1f1 and\/or the Janus kinase\/signal transducer and activator of transcription 3 transcriptional regulatory pathways are implicated in the leptin regulation of\n                    <jats:italic>Gh<\/jats:italic>\n                    or\n                    <jats:italic>Ghrhr<\/jats:italic>\n                    mRNAs. We then focused on potential actions by candidate microRNAs (miRNAs) with consensus binding sites on the 3' UTR of\n                    <jats:italic>Gh<\/jats:italic>\n                    or\n                    <jats:italic>Ghrhr<\/jats:italic>\n                    mRNAs. Somatotroph\n                    <jats:italic>Lepr<\/jats:italic>\n                    \u2010null deletion mutants expressed elevated levels of miRNAs including miR1197\u20103p (in females), miR103\u20103p and miR590\u20103p (both sexes), which bind\n                    <jats:italic>Gh<\/jats:italic>\n                    mRNA, or miRNA\u2010325\u20103p (elevated in both sexes), which binds\n                    <jats:italic>Ghrhr<\/jats:italic>\n                    mRNA. This elevation indicates repression of translation in the absence of LEPR. In addition, after detecting binding sites for Musashi on\n                    <jats:italic>Tshb<\/jats:italic>\n                    and\n                    <jats:italic>Prl<\/jats:italic>\n                    3' UTR, we determined that Musashi1 repressed translation of both mRNAs in in vitro fluc assays and that\n                    <jats:italic>Prl<\/jats:italic>\n                    mRNA was enriched in Musashi immunoprecipitation assays. Finally, we tested ghrelin actions to determine whether its nitric oxide\u2010mediated signalling pathways would restore somatotroph functions in deletion mutants. Ghrelin did not restore either GHRH binding or GH secretion in vitro. These studies show an unexpectedly broad role for leptin with respect to maintaining somatotroph functions, including the regulation of PRL and TSH in subsets of somatotrophs that may be progenitor cells.\n                  <\/jats:p>","DOI":"10.1111\/jne.12883","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T17:53:43Z","timestamp":1592416423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Metabolic signalling to somatotrophs: Transcriptional and post\u2010transcriptional mediators"],"prefix":"10.1111","volume":"32","author":[{"given":"Melody L.","family":"Allensworth\u2010James","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Odle","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juchan","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex N.","family":"LaGasse","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany K.","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda L.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anessa C.","family":"Haney","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie C.","family":"MacNicol","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus M.","family":"MacNicol","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3764-1373","authenticated-orcid":false,"given":"Gwen V.","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Developmental Sciences University of Arkansas for Medical Sciences Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199804000-00007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009159"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1626"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0441"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00584.2006"},{"key":"e_1_2_7_7_1","first-page":"4634","article-title":"Multiple signaling pathways convey central and peripheral signals to regulate pituitary function: Lessons from human and non\u2010human primate models","author":"Vazquez\u2010Borrego MC","year":"2018","journal-title":"Mol Cell Endocrinol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43537"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.46.Suppl_S17"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6231"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1420066"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000127262"},{"key":"e_1_2_7_13_1","first-page":"203","article-title":"Effects of 22K or 20K human growth hormone on lipolysis, leptin production in adipocytes in the presence and absence of human growth hormone binding protein","volume":"54","author":"Asada N","year":"2000","journal-title":"Horm Res"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012978525492"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410100407"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00258.2006"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.7A7214.2007"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2015-1198"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0498"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1331"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-2254"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1472"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-127"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00586"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1620177"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-119-2-629"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.134.2.990"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.300681"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.1.14388"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12861-015-0064-y"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.16.5328"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc.2010.005"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100814-125446"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09171"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.12.3888-3900.2001"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.09.003"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78173"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.573"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10112"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00750"}],"container-title":["Journal of Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjne.12883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.12883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jne.12883","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.12883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T15:12:59Z","timestamp":1693840379000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jne.12883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,13]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/jne.12883"],"URL":"https:\/\/doi.org\/10.1111\/jne.12883","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNE.12883\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v3\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.12883\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0953-8194","1365-2826"],"issn-type":[{"value":"0953-8194","type":"print"},{"value":"1365-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,13]]},"assertion":[{"value":"2020-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12883"}}