{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:47:24Z","timestamp":1788922044438,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"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":"crossref","award":["32573493"],"award-info":[{"award-number":["32573493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32230107"],"award-info":[{"award-number":["32230107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Taishan Young Scholar Project of Shandong Province","award":["tsqn202211266"],"award-info":[{"award-number":["tsqn202211266"]}]},{"DOI":"10.13039\/501100012428","name":"Central Public-interest Scientific Institution Basal Research Fund, CAFS","doi-asserted-by":"crossref","award":["2023TD20"],"award-info":[{"award-number":["2023TD20"]}],"id":[{"id":"10.13039\/501100012428","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sexual size dimorphism (SSD) refers to the phenomenon where males and females of the same species exhibit differences in overall or partial body size, and it is widespread among mammals, birds, reptiles, and fish. Notably, this dimorphism is significantly influenced by the sexually dimorphic secretion of growth hormone (gh), a key pituitary-derived growth regulator. Commonly, the secretion of gh is positively regulated by glucagon family members such as growth hormone-releasing hormone (ghrh) and adenylate cyclase-activating polypeptide 1 (adcyap1). To explore the stimulators for pituitary hormones (especially gh) in the teleost, we performed genome-wide identification and functional characterization of the glucagon family on Chinese tongue sole (Cynoglossus semilaevis) that exhibits typical female-biased sexual size dimorphism. Four members of adcyap1\/vasoactive intestinal polypeptide(vip)\/ghrh family and ten members of their receptor family were identified. Expression pattern analysis revealed high expression of adenylate cyclase-activating polypeptide 1b (adcyap1b) and its receptors in the brain. Moreover, two alternative splice variants for the adcyap1b gene were discovered, resulting from the skipping of exon 4. Following the acquisition of the two eukaryotic recombinant protein splice variants (ADCYAP1b_tv1 and ADCYAP_tv2) from HEK 293T cells, incubation experiments were conducted using C. semilaevis pituitary cell line. The results demonstrated that both variants promoted the expression of gh, pro-opiomelanocortin (pomc), and corticoliberin (crh), but ADCYAP1b_tv1 had a significantly stronger effect and uniquely stimulated prolactin (prl) and somatolactin (sl). This study demonstrates a functional divergence between the two ADCYAP1b splice variants in teleosts, with ADCYAP1b_tv1 acting as a more potent and versatile pituitary hormone stimulator. Further research on their receptor-binding affinity and downstream signaling pathways would be valuable for exploring the mechanism underlying sexual size dimorphism.<\/jats:p>","DOI":"10.3390\/ijms27031225","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T15:48:30Z","timestamp":1769442510000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional Divergence of adcyap1b Splice Variants in Regulating Pituitary Hormone Expression in the Chinese Tongue Sole (Cynoglossus semilaevis)"],"prefix":"10.3390","volume":"27","author":[{"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"},{"name":"Graduate School of Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-0908","authenticated-orcid":false,"given":"Xihong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-9973","authenticated-orcid":false,"given":"Wenteng","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2135-090X","authenticated-orcid":false,"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20210251","DOI":"10.1098\/rsbl.2021.0251","article-title":"Sexual selection and sexual size dimorphism in animals","volume":"17","author":"Janicke","year":"2021","journal-title":"Biol. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fairbairn, D.J., Blanckenhorn, W.U., and Sz\u00e9kely, T. (2007). Sex, Size and Gender Roles: Evolutionary Studies of Sexual Size Dimorphism, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780199208784.001.0001"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1677\/JOE-10-0045","article-title":"The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins","volume":"206","author":"Ahmed","year":"2010","journal-title":"J. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1210\/en.2011-1982","article-title":"Sexual dimorphism of growth hormone in the hypothalamus: Regulation by estradiol","volume":"153","author":"Addison","year":"2012","journal-title":"Endocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1210\/en.2003-0006","article-title":"Growth hormone-releasing hormone (GHRH) neurons in GHRH-enhanced green fluorescent protein transgenic mice: A ventral hypothalamic network","volume":"144","author":"Balthasar","year":"2003","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.domaniend.2005.02.022","article-title":"The release of growth hormone (GH): Relation to the thyrotropic- and corticotropic axis in the chicken","volume":"29","author":"Geelissen","year":"2005","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1139\/o00-055","article-title":"Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish","volume":"78","author":"Wong","year":"2000","journal-title":"Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1677\/jme.0.0250157","article-title":"Molecular evolution of the growth hormone-releasing hormone\/pituitary adenylate cyclase-activating polypeptide gene family. Functional implication in the regulation of growth hormone secretion","volume":"25","author":"Montero","year":"2000","journal-title":"J. Mol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1038\/s42003-021-02476-5","article-title":"Estrogen mediates sex differences in preoptic neuropeptide and pituitary hormone production in medaka","volume":"4","author":"Yamashita","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0006-291X(89)91757-9","article-title":"Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells","volume":"164","author":"Miyata","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/0006-291X(90)92140-U","article-title":"Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38)","volume":"170","author":"Miyata","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1046\/j.1365-2826.1997.00580.x","article-title":"Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on hormone secretion from sheep pituitary cells in vitro","volume":"9","author":"Sawangjaroen","year":"1997","journal-title":"J. Neuroendocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1095\/biolreprod.112.105601","article-title":"Possible Role of PACAP and Its PAC1 Receptor in the Differential Regulation of Pituitary LHbeta- and FSHbeta-Subunit Gene Expression by Pulsatile GnRH Stimulation","volume":"88","author":"Kanasaki","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1677\/joe.0.1320107","article-title":"Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3","volume":"132","author":"Kanse","year":"1992","journal-title":"J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/ng.2890","article-title":"Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle","volume":"46","author":"Chen","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s10142-018-0595-y","article-title":"Transcriptomics analysis revealing candidate networks and genes for the body size sexual dimorphism of Chinese tongue sole (Cynoglossus semilaevis)","volume":"18","author":"Wang","year":"2018","journal-title":"Funct. Integr. Genom."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, N., Yang, Q., Wang, J., Shi, R., Li, M., Gao, J., Xu, W., Yang, Y., Chen, Y., and Chen, S. (2021). Integration of transcriptome and methylome highlights the roles of cell cycle and hippo signaling pathway in flatfish sexual size dimorphism. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.743722"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sun, Y., Li, X., Mai, J., Xu, W., Wang, J., Zhang, Q., and Wang, N. (2024). Three Copies of zbed1 Specific in Chromosome W Are Essential for Female-Biased Sexual Size Dimorphism in Cynoglossus semilaevis. Biology, 13.","DOI":"10.3390\/biology13030141"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, M., Shi, Y., Wang, Z., Chen, Z., Li, X., Xu, W., and Wang, N. (2025). Genome-Wide Identification and Characterization of gh\/prl\/sl Family in Cynoglossus semilaevis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041585"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000078103","article-title":"Leptin stimulates growth hormone secretion via a direct pituitary effect combined with a decreased somatostatin tone in a median eminence-pituitary perifusion study","volume":"79","author":"Saleri","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1210\/en.2007-0441","article-title":"Evidence that ghrelin is as potent as growth hormone (GH)-releasing hormone (GHRH) in releasing GH from primary pituitary cell cultures of a nonhuman primate (Papio anubis), acting through intracellular signaling pathways distinct from GHRH","volume":"148","author":"Kineman","year":"2007","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Devesa, J. (2021). The Complex World of Regulation of Pituitary Growth Hormone Secretion: The Role of Ghrelin, Klotho, and Nesfatins in It. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.636403"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nature03025","article-title":"Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype","volume":"431","author":"Jaillon","year":"2004","journal-title":"Nature"},{"key":"ref_24","first-page":"619","article-title":"The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)\/glucagon superfamily","volume":"21","author":"Sherwood","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1210\/endo.141.3.7347","article-title":"Pituitary adenylate cyclase-activating polypeptide gene expression regulated by a testis-specific promoter in germ cells during spermatogenesis","volume":"141","author":"Daniel","year":"2000","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1523\/JNEUROSCI.17-11-04045.1997","article-title":"Identification of endogenous sympathetic neuron pituitary adenylate cyclase-activating polypeptide (PACAP): Depolarization regulates production and secretion through induction of multiple propeptide transcripts","volume":"17","author":"Brandenburg","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1210\/endo.136.2.7835287","article-title":"Cloning and molecular characterization of complementary deoxyribonucleic acid corresponding to a novel form of pituitary adenylate cyclase-activating polypeptide messenger ribonucleic acid in the rat testis","volume":"136","author":"Hurley","year":"1995","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chang, C.W., Sung, Y.W., Hsueh, Y.W., Chen, Y.Y., Ho, M., Hsu, H.C., Yang, T.C., Lin, W.C., and Chang, H.M. (2022). Growth hormone in fertility and infertility: Mechanisms of action and clinical applications. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1040503"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ipsa, E., Cruzat, V.F., Kagize, J.N., Yovich, J.L., and Keane, K.N. (2019). Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00777"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"T99","DOI":"10.1530\/JME-15-0289","article-title":"60 YEARS of POMC: Transcriptional and epigenetic regulation of POMC gene expression","volume":"56","author":"Drouin","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/mrd.23177","article-title":"Increase of cortisol levels after temperature stress activates dmrt1a causing female-to-male sex reversal and reduced germ cell number in medaka","volume":"86","author":"Adolfi","year":"2019","journal-title":"Mol. Reprod. Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1152\/physrev.2000.80.4.1523","article-title":"Prolactin: Structure, Function, and Regulation of Secretion","volume":"80","author":"Freeman","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1023\/A:1018708704335","article-title":"Prolactin and mammary gland development","volume":"4","author":"Horseman","year":"1999","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"10661","DOI":"10.1073\/pnas.0401278101","article-title":"Somatolactin selectively regulates proliferation and morphogenesis of neural-crest derived pigment cells in medaka","volume":"101","author":"Fukamachi","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:28:01Z","timestamp":1769578081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031225"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031225","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]}}}