{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:39:06Z","timestamp":1762177146534,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T00:00:00Z","timestamp":1545782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31602130; 31500374; 31472267"],"award-info":[{"award-number":["31602130; 31500374; 31472267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidermal growth factor (EGF) is a potent regulator of cell function in many cell types. In mammals, the EGF\/EGFR system played an important role in both pituitary physiology and pathology. However, it is not clear about the pituitary action of EGF in lower vertebrates. In this study, using grass carp as a model, we found that EGF could stimulate NK3R mRNA and protein expression through pituitary ErbB1 and ErbB2 coupled to MEK\/ERK and PI3K\/Akt\/mTOR pathways. In addition, EGF could also induce pituitary somatolactin \u03b1 (SL\u03b1) secretion and mRNA expression in a dose- and time-dependent manner in vivo and in vitro. The stimulatory actions of EGF on SL\u03b1 mRNA expression were also mediated by PI3K\/Akt\/mTOR and MEK\/ERK pathways coupled to ErbB1 and ErbB2 activation. Our previous study has reported that neurokinin B (NKB) could also induce SL\u03b1 secretion and mRNA expression in carp pituitary cells. In the present study, interestingly, we found that EGF could significantly enhance NKB-induced SL\u03b1 mRNA expression. Further studies found that NK3R antagonist SB222200 could block EGF-induced SL\u03b1 mRNA expression, indicating an NK3R requirement. Furthermore, cAMP\/PKA inhibitors and PLC\/PKC inhibitors could both abolish EGF- and EGF+NKB-induced SL\u03b1 mRNA expression, which further supported that EGF-induced SL\u03b1 mRNA expression is NK3R dependent.<\/jats:p>","DOI":"10.3390\/ijms20010091","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T11:31:21Z","timestamp":1545823881000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["NK3R Mediates the EGF-Induced SL\u03b1 Secretion and mRNA Expression in Grass Carp Pituitary"],"prefix":"10.3390","volume":"20","author":[{"given":"Xiangfeng","family":"Qin","sequence":"first","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1039-7729","authenticated-orcid":false,"given":"Cheng","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-3829","authenticated-orcid":false,"given":"Xiaoyun","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaohua","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongyao","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangfu","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hubei Province Engineering Laboratory for Pond Aquaculture, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1016\/S0021-9258(18)32668-1","article-title":"Epidermal growth factor and thyrotropin-releasing hormone interact synergistically with calcium to regulate prolactin mRNA levels","volume":"258","author":"White","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1210\/endo.136.4.7895669","article-title":"Corticotropin-releasing hormone and epidermal growth factor: Mitogens for anterior pituitary corticotropes","volume":"136","author":"Childs","year":"1995","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0196-9781(86)90059-8","article-title":"Distribution of epidermal growth factor binding sites in the adult rat anterior pituitary gland","volume":"7","author":"Chabot","year":"1986","journal-title":"Peptides"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1210\/jcem-65-2-275","article-title":"Epidermal growth factor-binding sites, present in normal human and rat pituitaries, are absent in human pituitary adenomas","volume":"65","author":"Birman","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1210\/endo.136.5.7720677","article-title":"Epidermal growth factor and transforming growth factor-\u03b1 messenger ribonucleic acids and their receptors in the rat anterior pituitary: Localization and regulation","volume":"136","author":"Fan","year":"1995","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1210\/endo.136.3.7867595","article-title":"Differential regulation of epidermal growth factor and transforming growth factor-\u03b1 messenger ribonucleic acid in the rat anterior pituitary and hypothalamus induced by stresses","volume":"136","author":"Fan","year":"1995","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1677\/joe.0.1410547","article-title":"Human pituitary somatotropes express transforming growth factor-\u03b1 and its receptor","volume":"141","author":"Finley","year":"1994","journal-title":"J. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/0046-8177(92)90055-8","article-title":"Transforming growth factor-\u03b1 in normal and neoplastic human endocrine tissues","volume":"23","author":"Driman","year":"1992","journal-title":"Hum. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/BF02739916","article-title":"Localization of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) in human pituitary adenomas and nontumorous pituitaries: An immunocytochemical study","volume":"7","author":"Kontogeorgos","year":"1996","journal-title":"Endocr. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R197","DOI":"10.1530\/ERC-11-0066","article-title":"Expression and function of ErbB receptors and ligands in the pituitary","volume":"18","author":"Cooper","year":"2011","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1097\/00001756-199507100-00010","article-title":"Epidermal growth factor: A potential paracrine and autocrine system within the pituitary","volume":"6","author":"Mouihate","year":"1995","journal-title":"Neuroreport"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0303-7207(88)90045-7","article-title":"Epidermal growth factor stimulates luteinizing hormone and arachidonic acid release in rat pituitary cells","volume":"57","author":"Przylipiak","year":"1988","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1677\/joe.0.1460495","article-title":"Estrogen increases the release of epidermal growth factor from individual pituitary cells in female rats","volume":"146","author":"Mouihate","year":"1995","journal-title":"J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0024-3205(95)02263-5","article-title":"EGF release by rat gonadotroph cells: Characteristics and effects of LHRH","volume":"58","author":"Mouihate","year":"1996","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1677\/joe.0.1480319","article-title":"Identification of epidermal growth factor-secreting cells in the anterior pituitary of lactating female rats","volume":"148","author":"Mouihate","year":"1996","journal-title":"J. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1046\/j.0007-1331.2002.00786.x","article-title":"Mitogen-activated protein kinase mediates epidermal growth factor-induced morphogenesis in pituitary GH3 cells","volume":"14","author":"Lewis","year":"2002","journal-title":"J. Neuroendocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ygcen.2008.11.020","article-title":"Differential regulation of gonadotropins (FSH and LH) and growth hormone (GH) by neuroendocrine, endocrine, and paracrine factors in the zebrafish-An in vitro approach","volume":"160","author":"Lin","year":"2009","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1073\/pnas.87.11.4330","article-title":"cDNA cloning of somatolactin, a pituitary protein related to growth hormone and prolactin","volume":"87","author":"Ono","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1677\/joe.0.1820509","article-title":"Cloning of somatolactin alpha and beta cDNAs in zebrafish and phylogenetic analysis of two distinct somatolactin subtypes in fish","volume":"182","author":"Zhu","year":"2004","journal-title":"J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1477-7827-6-42","article-title":"Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: Seasonal expression profile in pituitary and ovary of maturing female broodstock","volume":"6","author":"Benedet","year":"2008","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E477","DOI":"10.1152\/ajpendo.90386.2008","article-title":"Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin \u03b1 and \u03b2 gene expression","volume":"295","author":"Jiang","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/jez.1734","article-title":"Effect of stress during handling, seawater acclimation, confinement, and induced spawning on plasma ion levels and somatolactin-expressing cells in mature female Liza ramada","volume":"317","author":"Khalil","year":"2012","journal-title":"J. Exp. Zool. A"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sasano, Y., Yoshimura, A., and Fukamachi, S. (2012). Reassessment of the function of somatolactin alpha in lipid metabolism using medaka mutant and transgenic strains. BMC Genet., 13.","DOI":"10.1186\/1471-2156-13-64"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbpa.2012.09.019","article-title":"Profiles of mRNA expression for prolactin, growth hormone, and somatolactin in Japanese eels, Anguilla japonica: The effect of salinity, silvering and seasonal change","volume":"164","author":"Sudo","year":"2013","journal-title":"Comp. Biochem. Physiol. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1210\/en.2014-1105","article-title":"Novel pituitary actions of TAC3 gene products in fish model: -Receptor specificity and signal transduction for prolactin and somatolactin alpha regulation by neurokinin B (NKB) and NKB-related peptide in carp pituitary cells","volume":"155","author":"Hu","year":"2014","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1210\/jc.2009-0551","article-title":"Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor","volume":"94","author":"Guran","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ng.306","article-title":"TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction","volume":"41","author":"Topaloglu","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1210\/jc.2009-2600","article-title":"TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans","volume":"95","author":"Young","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10269","DOI":"10.1073\/pnas.1119165109","article-title":"Neurokinin Bs and neurokinin B receptors in zebrafish-potential role in controlling fish reproduction","volume":"109","author":"Biran","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.mce.2012.04.007","article-title":"The evolution of tachykinin\/tachykinin receptor (TAC\/TACR) in vertebrates and molecular identification of the TAC3\/TACR3 system in zebrafish (Danio rerio)","volume":"361","author":"Zhou","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1210\/en.2016-1354","article-title":"Neurokinin B exerts direct effects on the ovary to stimulate estradiol production","volume":"157","author":"Qi","year":"2016","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.mce.2010.04.008","article-title":"EGF receptor activation by GPCRs: An universal pathway reveals different versions","volume":"331","author":"Liebmann","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1095\/biolreprod.104.028399","article-title":"Cloning of epidermal growth factor (EGF) and EGF receptor from the zebrafish ovary: Evidence for EGF as a potential paracrine factor from the oocyte to regulated activin\/follistatin system in the follicle cells","volume":"71","author":"Wang","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/300192a0","article-title":"Epidermal growth factor rapidly stimulates prolactin gene transcription","volume":"300","author":"Murdoch","year":"1982","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1210\/en.2008-0756","article-title":"Estrogen receptor-\u03b1 mediates the epithermal growth factor-stimulated prolactin expression and release in lactotrophs","volume":"150","author":"Dunckely","year":"2009","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1210\/endo-115-2-556","article-title":"Epidermal growth factor stimulates growth hormone secretion from superfused rat adenohypophyseal fragments","volume":"115","author":"Ikeda","year":"1984","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S1546-5098(09)28005-8","article-title":"The neuroendocrine regulation of prolactin and somatolactin secretion in fish","volume":"28","author":"Kawauchi","year":"2009","journal-title":"Fish Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5526","DOI":"10.1073\/pnas.071060598","article-title":"The role of distinct p185neu extracellular subdomains for dimerization with the epidermal growth factor (EGF) receptor and EGF-mediated signaling","volume":"98","author":"Kumagai","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1073\/pnas.1633546100","article-title":"Role of extracellular subdomains of p185c-neu and the epidermal growth factor receptor in ligand independent association and transactivation","volume":"100","author":"Kumagai","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1073\/pnas.91.4.1500","article-title":"Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: A mechanism of interreceptor kinase activation and transphosphorylation","volume":"91","author":"Qian","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V","article-title":"Specificity within the EGF family\/ErbB receptor family signaling network","volume":"20","author":"Riese","year":"1998","journal-title":"Bioessays"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.1128\/MCB.15.12.6496","article-title":"New differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2","volume":"15","author":"Beerli","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1128\/MCB.15.3.1182","article-title":"Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling","volume":"15","author":"Beerli","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/j.1460-2075.1996.tb00356.x","article-title":"ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer","volume":"15","author":"Karunagaran","year":"1996","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/0092-8674(90)90697-D","article-title":"Intermolecular association of the p185neu protein and EGF receptor modulates EGF receptor function","volume":"61","author":"Wada","year":"1990","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14661","DOI":"10.1016\/S0021-9258(17)36676-0","article-title":"Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin","volume":"269","author":"Sliwkowski","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2174\/0929866511320060002","article-title":"Insight into molecular and functional diversity of tachykinins and their receptors","volume":"20","author":"Satake","year":"2013","journal-title":"Protein Pept. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server","volume":"31","author":"Schwede","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1006\/gcen.1997.7045","article-title":"Somatostatin inhibits (D-Arg6, Pro9-NEt) salmon gonadotropin-releasing hormone- and dopamine D1-stimulated growth hormone release from perifused pituitary cells of Chinese grass carp, Ctenopharyngodon idellus","volume":"110","author":"Wong","year":"1998","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3389\/fendo.2018.00308","article-title":"Pituitary action of E2 in prepubertal grass carp: Receptor specificity and signal transduction for luteinizing hormone and follicle-stimulating hormone regulation","volume":"9","author":"Qin","year":"2018","journal-title":"Front. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:36:14Z","timestamp":1760196974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,26]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20010091"],"URL":"https:\/\/doi.org\/10.3390\/ijms20010091","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,12,26]]}}}