{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:40:14Z","timestamp":1762177214336,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"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"],"award-info":[{"award-number":["31602130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In mammals, the tachykinin 3 (TAC3)\/tachykinin receptor 3 (TACR3) systems have been confirmed to play an important role in the regulation of puberty onset. Using grass carp pituitary cells as the model, our recent study found that the TAC3 gene products could significantly induce somatolactin \u03b1 (SL\u03b1) synthesis and secretion via TACR3 activation. In the present study, we seek to examine if pituitary TACR3 can serve as a regulatory target and contribute to TAC3 interactions with other SL\u03b1 regulators. Firstly, grass carp TACR3 was cloned and tissue distribution showed that it could be highly detected in grass carp pituitary. Using HEK293 cells as the model, functional expression also revealed that grass carp TACR3 exhibited ligand binding selectivity and post-receptor signaling highly comparable to its mammalian counterpart. Using grass carp pituitary cells as the model, TACR3 mRNA expression could be stimulated by insulin-like growth factor (IGF)-I and -II via the IGF-I receptor coupled to phosphatidylinositol-3-kinase (PI3K)\/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Interestingly, IGF-I\/-II cotreatment could also significantly enhance TAC3-induced SL\u03b1 mRNA expression and the potentiating effect was dependent on TACR3 expression and activation of adenylate cyclase (AC)\/cAMP\/protein kinase A (PKA), phospholipase C (PLC)\/inositol 1,4,5-triphosphate (IP3)\/protein kinase C (PKC), and Ca2+\/calmodulin (CaM)\/calmodulin-dependent protein kinase II (CaMK-II) cascades. Besides, IGF-I-induced Akt phosphorylation but not MEK, extracellular signal-regulated kinase (ERK1\/2), and P38MAPK phosphorylation was notably enhanced by TACR3 activation. These results, as a whole, suggest that the potentiating effect of IGFs on TAC3 gene products-induced SL\u03b1 mRNA expression was mediated by TACR3 upregulation and functional crosstalk of post-receptor signaling in the pituitary.<\/jats:p>","DOI":"10.3390\/cells8080887","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T03:59:26Z","timestamp":1565755166000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["IGFs Potentiate TAC3-induced SL\u03b1 Expression via Upregulation of TACR3 Expression in Grass Carp Pituitary Cells"],"prefix":"10.3390","volume":"8","author":[{"given":"Guangfu","family":"Hu","sequence":"first","affiliation":[{"name":"College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mulan","family":"He","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy K. W.","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongyao","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anderson O. L.","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,13]]},"reference":[{"key":"ref_1","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_2","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 rxtracellular loop of the neurokinin B receptor","volume":"94","author":"Guran","year":"2009","journal-title":"J. Clin. Endocr. Metab."},{"key":"ref_3","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_4","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_5","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_6","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_7","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_8","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_9","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/bies.20293","article-title":"From 2R to 3R: Evidence for a fish-specific genome duplication (FSGD)","volume":"27","author":"Meyer","year":"2005","journal-title":"Bioessays"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/0-387-26274-1_1","article-title":"Basic physiology of the growth hormone\/insulin-like growth factor axis","volume":"567","author":"Frago","year":"2005","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","first-page":"205","article-title":"The insulin-like growth factor system","volume":"4","year":"2003","journal-title":"Exp. Diabesity Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s004670000334","article-title":"Growth hormone axis overview: Somatomedin hypothesis","volume":"14","author":"Daughaday","year":"2000","journal-title":"Pediatr. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1271\/bbb.64.1553","article-title":"Growth regulation by insulin-like growth factor-I in fish","volume":"64","author":"Moriyama","year":"2000","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000054327","article-title":"Long-term inhibitory effects of somatostatin and insulin-like growth factor 1 on growth hormone release by serum free primary culture of pituitary cells from European eel (Anguilla anguilla)","volume":"67","author":"Rousseau","year":"1998","journal-title":"Neuroendocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1210\/en.2004-1508","article-title":"Modulation of calmodulin gene expression as a novel mechanism for growth hormone feedback control by insulin-like growth factor in grass carp pituitary cells","volume":"146","author":"Huo","year":"2005","journal-title":"Endocrinology"},{"key":"ref_16","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_17","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_18","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_19","doi-asserted-by":"crossref","first-page":"E1208","DOI":"10.1152\/ajpendo.00347.2011","article-title":"Insulin-like growth factor as a novel stimulator for somatolactin secretion and synthesis in carp pituitary cells via activation of MAPK cascades","volume":"301","author":"Jiang","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1158\/1078-0432.CCR-09-2229","article-title":"Crosstalk between insulin\/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: A novel target for the antidiabetic drug metformin in pancreatic cancer","volume":"16","author":"Rozengurt","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1210\/en.2006-1711","article-title":"Insulin potentiates Ca2+ signaling and phosphatidylinositol 4,5-bisphosphate hydrolysis induced by Gq protein-coupled agonists through an mTOR-dependent pathway","volume":"148","author":"Kisfalvi","year":"2007","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1158\/0008-5472.CAN-09-0418","article-title":"Metformin disrupts crosstalk between G protein-coupled receptor and isulin receptor signaling systems and inhibits pancreatic cancer growth","volume":"69","author":"Kisfalvi","year":"2009","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1076\/ceyr.16.3.275.15409","article-title":"Combined effects of substance P and insulin-like growth factor-1 on corneal epithelial wound closure of rabbit in vivo","volume":"16","author":"Nakamura","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1006\/bbrc.1998.8704","article-title":"Up-regulation of integrin \u03b15 expression by combination of substance P and insulin-like growth factor-1 in rabbit corneal epithelial cells","volume":"246","author":"Nakamura","year":"1998","journal-title":"Biochem. Bioph. Res. Co."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1167\/iovs.04-0775","article-title":"Sensitizing effect of substance P on corneal epithelial migration induced by IGF-I, fibronectin, or interleukin-6","volume":"46","author":"Yamada","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36102","DOI":"10.1038\/srep36102","article-title":"Novel functional role of NK3R expression in the potentiating effects on somatolactin \u03b1 autoregulation in grass carp pituitary cells","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/1875397301004010084","article-title":"Luciferase reporter assay system for deciphering GPCR pathways","volume":"4","author":"Cheng","year":"2010","journal-title":"Curr. Chem. Genomics"},{"key":"ref_30","first-page":"e2732","article-title":"A calcium bioluminescence assay for functional analysis of mosquito (Aedes aegypti) and Tick (Rhipicephalus microplus) G protein-coupled receptors","volume":"50","author":"Lu","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1210\/en.2004-0163","article-title":"Novel aspects of growth hormone (GH) autoregulation: GH-induced GH gene expression in grass carp pituitary cells through autocrine\/paracrine mechanisms","volume":"145","author":"Zhou","year":"2004","journal-title":"Endocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1210\/en.2012-1574","article-title":"Suppression of the GnRH pulse generator by neurokinin B involves a kappa-opioid receptor-dependent mechanism","volume":"153","author":"Grachev","year":"2012","journal-title":"Endocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1210\/en.2013-1331","article-title":"Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control activity of the GnRH pulse generator in ewes","volume":"154","author":"Goodman","year":"2013","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1210\/en.2013-1268","article-title":"Regulation of arcuate neurons coexpressing kisspeptin, neurokinin B, and dynorphin by modulators of neurokinin 3 and \u03ba-opioid receptors in adult male mice","volume":"154","author":"Ruka","year":"2013","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00018-007-7148-1","article-title":"Tachykinins and their functions in the gastrointestinal tract","volume":"65","author":"Shimizu","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","first-page":"R1683","article-title":"Canine intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors","volume":"275","author":"Thompson","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/sj.bjp.0705042","article-title":"Implication of nigral tachykinin NK3 receptors in the maintenance of hypertension in spontaneously hypertensive rats: A pharmacologic and autoradiographic study","volume":"138","author":"Lessard","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0014-2999(87)90363-3","article-title":"The rat isolated portal vein: A preparation sensitive to neurokinins, particularly neurokinin B","volume":"134","author":"Mastrangelo","year":"1987","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.fertnstert.2012.02.021","article-title":"Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract","volume":"97","author":"Pinto","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1477-7827-8-104","article-title":"Autocrine regulation of human sperm motility by tachykinins","volume":"8","author":"Pinto","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/humrep\/dem069","article-title":"A role for tachykinins in the regulation of human sperm motility","volume":"22","author":"Ravina","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.2174\/0929867043364748","article-title":"Tachykinins and tachykinin receptors: Structure and activity relationships","volume":"11","author":"Almeida","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0021-9258(19)40095-1","article-title":"Cloning and expression of a rat neurokinin-K receptor cDNA","volume":"265","author":"Shigemoto","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1556\/APhysiol.92.2005.2.1","article-title":"The insulin-like growth factor system: IGFs, IGF binding proteins and IGFBP-proteases","volume":"92","author":"Lelbach","year":"2005","journal-title":"Acta Physiol Hung."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1210\/endo.141.8.7616","article-title":"Insulin-like growth factor I disparately regulates prolactin and growth hormone synthesis and secretion: Studies using the teleost pituitary model","volume":"141","author":"Fruchtman","year":"2000","journal-title":"Endocrinology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1095\/biolreprod63.3.865","article-title":"Insulin-like growth factor I increases follicle-stimulating hormone (FSH) content and gonadotropin-releasing hormone-stimulated FSH release from coho salmon pituitary cells in vitro","volume":"63","author":"Baker","year":"2000","journal-title":"Biol Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1677\/joe.0.1590043","article-title":"Insulin-like growth factor-I stimulates gonadotropin production from eel pituitary cells: A possible metabolic signal for induction of puberty","volume":"159","author":"Huang","year":"1998","journal-title":"J. Endocrinol."},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.regpep.2007.08.018","article-title":"Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on prolactin and somatolactin release from the goldfish pituitary in vitro","volume":"145","author":"Matsuda","year":"2008","journal-title":"Regul. Pept."},{"key":"ref_51","first-page":"755","article-title":"Somatostatin-28 inhibitory action on somatolactin \u03b1 and \u03b2 gene expression in goldfish","volume":"307","author":"Jiang","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E176","DOI":"10.1152\/ajpendo.00455.2012","article-title":"Signal transduction mechanisms for autocrine\/paracrine regulation of somatolactin-\u03b1 secretion and synthesis in carp pituitary cells by somatolactin-\u03b1 and -\u03b2","volume":"304","author":"Jiang","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6364","DOI":"10.1158\/1078-0432.CCR-07-4879","article-title":"The type 1 insulin-like growth factor receptor pathway","volume":"14","author":"Chitnis","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JME-11-0022","article-title":"Signaling by insulin and IGF receptors: Supporting acts and new players","volume":"47","author":"Siddle","year":"2011","journal-title":"J. Mol. Endocrinol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/8\/887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:51Z","timestamp":1760188251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/8\/887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,13]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["cells8080887"],"URL":"https:\/\/doi.org\/10.3390\/cells8080887","relation":{},"ISSN":["2073-4409"],"issn-type":[{"type":"electronic","value":"2073-4409"}],"subject":[],"published":{"date-parts":[[2019,8,13]]}}}