{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T03:08:38Z","timestamp":1787281718949,"version":"build-2736575974"},"reference-count":35,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273108"],"award-info":[{"award-number":["32273108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["2024NSFSC0380"],"award-info":[{"award-number":["2024NSFSC0380"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Low temperatures significantly impact growth in ectothermic vertebrates, though the underlying mechanisms remain poorly understood. This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) channels in mediating low-temperature effects on growth performance and GH resistance in Nile tilapia (Oreochromis niloticus). Prolonged exposure to low temperature (16 \u00b0C for 35 days) impaired growth performance and induced GH resistance, characterized by elevated serum GH levels and decreased IGF-1 levels. Molecular analysis revealed tissue-specific upregulation of TRPA1 expression in the pituitary and liver under low-temperature conditions, concurrent with alterations in GH\/IGF-1 axis-related gene expression. Pharmacological modulation of TRPA1 using an agonist mimicked low-temperature effects on the GH\/IGF-1 axis, while an antagonist reversed cold-induced hormonal changes. In vitro experiments with tilapia hepatocytes demonstrated that TRPA1 activation decreased IGF-1 expression through calcium ion\/calmodulin-dependent pathways and disrupted GH-induced JAK2\/STAT5 signaling. Additionally, TRPA1 activation induced GH receptor degradation primarily through lysosomal pathways, with partial involvement of proteasomal mechanisms. This study is the first to reveal that TRPA1 channels play a crucial role in mediating the effects of low temperature on GH resistance in fish, providing new insights into temperature regulation of endocrine function. The evolutionary conservation of TRPA1 and the GH\/IGF-1 axis suggests potential relevance to stress-induced endocrine dysfunction in other vertebrates, including mammals.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf013","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T08:30:23Z","timestamp":1737966623000},"source":"Crossref","is-referenced-by-count":10,"title":["Mechanisms of Low Temperature-induced GH Resistance via TRPA1 Channel Activation in Male Nile Tilapia"],"prefix":"10.1210","volume":"166","author":[{"given":"Zhikai","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2335-7956","authenticated-orcid":false,"given":"Quan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University , Chengdu 610065 P.R. ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"6","key":"2025020410355345400_bqaf013-B1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S1043-2760(01)00423-4","article-title":"Signaling pathways activated by the growth hormone receptor","volume":"12","author":"Herrington","year":"2001","journal-title":"Trends Endocrinol Metab"},{"key":"2025020410355345400_bqaf013-B2","doi-asserted-by":"crossref","first-page":"111035","DOI":"10.1016\/j.mce.2020.111035","article-title":"Disorders of IGFs and IGF-1R signaling pathways","volume":"518","author":"Forbes","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"2025020410355345400_bqaf013-B3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fendo.2011.00095","article-title":"Genetic defects in the growth hormone-IGF-I axis causing growth hormone insensitivity and impaired linear growth","volume":"2","author":"Savage","year":"2011","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"8","key":"2025020410355345400_bqaf013-B4","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.2337\/diabetes.50.8.1891","article-title":"Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes","volume":"50","author":"Takano","year":"2001","journal-title":"Diabetes"},{"issue":"5","key":"2025020410355345400_bqaf013-B5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ghir.2005.07.001","article-title":"Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity","volume":"15","author":"Dominici","year":"2005","journal-title":"Growth Horm IGF Res"},{"issue":"10","key":"2025020410355345400_bqaf013-B6","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.3390\/ijms18102046","article-title":"Characterization of growth hormone resistance in experimental and ulcerative colitis","volume":"18","author":"Soendergaard","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"22","key":"2025020410355345400_bqaf013-B7","doi-asserted-by":"crossref","first-page":"10272","DOI":"10.1073\/pnas.88.22.10272","article-title":"Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome","volume":"88","author":"Duquesnoy","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"2025020410355345400_bqaf013-B8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0950-351X(96)80545-3","article-title":"Acquired growth hormone resistance in catabolic states","volume":"10","author":"Jenkins","year":"1996","journal-title":"Baillieres Clin Endocrinol Metab"},{"issue":"1","key":"2025020410355345400_bqaf013-B9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0016-6480(03)00156-4","article-title":"Environmental temperature increases plasma GH levels independently of nutritional status in rainbow trout (Oncorhynchus mykiss)","volume":"133","author":"Gabillard","year":"2003","journal-title":"Gen Comp Endocrinol"},{"issue":"2","key":"2025020410355345400_bqaf013-B10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0016-6480(03)00167-9","article-title":"Effects of environmental temperature on IGF1, IGF2, and IGF type I receptor expression in rainbow trout (Oncorhynchus mykiss)","volume":"133","author":"Gabillard","year":"2003","journal-title":"Gen Comp Endocrinol"},{"issue":"4","key":"2025020410355345400_bqaf013-B11","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1073\/pnas.0808487106","article-title":"TRPA1 acts as a cold sensor in vitro and in vivo","volume":"106","author":"Karashima","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2025020410355345400_bqaf013-B12","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0092-8674(03)00158-2","article-title":"ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures","volume":"112","author":"Story","year":"2003","journal-title":"Cell"},{"issue":"10","key":"2025020410355345400_bqaf013-B13","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.cellsig.2005.12.009","article-title":"TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD","volume":"18","author":"Stokes","year":"2006","journal-title":"Cell Signal"},{"key":"2025020410355345400_bqaf013-B14","doi-asserted-by":"crossref","first-page":"112333","DOI":"10.1016\/j.mce.2024.112333","article-title":"Low temperature inhibits food intake via TRPA1 channel activation in Nile tilapia (Oreochromis niloticus)","volume":"592","author":"Cao","year":"2024","journal-title":"Mol Cell Endocrinol"},{"issue":"2","key":"2025020410355345400_bqaf013-B15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jtherbio.2007.05.007","article-title":"Effects of water temperature on growth and sex ratio of juvenile Nile tilapia Oreochromis niloticus (Linnaeus) reared in geothermal waters in southern Tunisia","volume":"33","author":"Azaza","year":"2008","journal-title":"J Therm Biol"},{"issue":"18","key":"2025020410355345400_bqaf013-B16","doi-asserted-by":"crossref","first-page":"9499","DOI":"10.1073\/pnas.93.18.9499","article-title":"Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways","volume":"93","author":"Sengupta","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"2025020410355345400_bqaf013-B17","doi-asserted-by":"crossref","first-page":"e42454","DOI":"10.1371\/journal.pone.0042454","article-title":"Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation","volume":"7","author":"Nassini","year":"2012","journal-title":"PLoS One"},{"key":"2025020410355345400_bqaf013-B18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.mce.2016.09.030","article-title":"Irisin inhibition of growth hormone secretion in cultured tilapia pituitary cells","volume":"439","author":"Lian","year":"2017","journal-title":"Mol Cell Endocrinol"},{"issue":"2","key":"2025020410355345400_bqaf013-B19","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/are.14914","article-title":"The effects of four plant extracts on growth, sex reversal, immunological and haemato-biochemical parameters in Nile tilapia, Oreochmomis niloticus (Linnaeus, 1758)","volume":"52","author":"Ghosal","year":"2021","journal-title":"Aquac Res"},{"issue":"1","key":"2025020410355345400_bqaf013-B20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/JME-15-0207","article-title":"Adropin induction of lipoprotein lipase expression in tilapia hepatocytes","volume":"56","author":"Lian","year":"2016","journal-title":"J Mol Endocrinol"},{"key":"2025020410355345400_bqaf013-B21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.fsi.2021.12.039","article-title":"Interleukin-6 mediates lipopolysaccharide-inhibited irisin secretion in Nile tilapia (Oreochromis niloticus)","volume":"121","author":"Yan","year":"2022","journal-title":"Fish Shellfish Immunol"},{"issue":"4","key":"2025020410355345400_bqaf013-B22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))","volume":"25","author":"Livak","year":"2001","journal-title":"Method. Methods"},{"key":"2025020410355345400_bqaf013-B23","doi-asserted-by":"crossref","first-page":"629077","DOI":"10.3389\/fendo.2020.629077","article-title":"Signal transduction mechanisms for glucagon-induced somatolactin secretion and gene expression in Nile tilapia (oreochromis niloticus) pituitary cells","volume":"11","author":"Zhang","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025020410355345400_bqaf013-B24","doi-asserted-by":"crossref","first-page":"108549","DOI":"10.1016\/j.fsi.2023.108549","article-title":"Molecular characterization and immune functions of lipasin in Nile tilapia (Oreochromis niloticus): involvement in the regulation of tumor necrosis factor-alpha secretion","volume":"133","author":"Dong","year":"2023","journal-title":"Fish Shellfish Immunol"},{"issue":"6","key":"2025020410355345400_bqaf013-B25","doi-asserted-by":"crossref","first-page":"R609","DOI":"10.1152\/ajpregu.00027.2022","article-title":"Tilapia prolactin cells are thermosensitive osmoreceptors","volume":"322","author":"Woo","year":"2022","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"12","key":"2025020410355345400_bqaf013-B26","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1016\/j.celrep.2017.11.083","article-title":"Molecular prerequisites for diminished cold sensitivity in ground squirrels and hamsters","volume":"21","author":"Matos-Cruz","year":"2017","journal-title":"Cell Rep"},{"issue":"3","key":"2025020410355345400_bqaf013-B27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/chemse\/bjv091","article-title":"Sensitivities of two zebrafish TRPA1 paralogs to chemical and thermal stimuli analyzed in heterologous expression systems","volume":"41","author":"Oda","year":"2016","journal-title":"Chem Senses"},{"issue":"4","key":"2025020410355345400_bqaf013-B28","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/WNR.0000000000000939","article-title":"Sensitivity of Takifugu TRPA1 to thermal stimulations analyzed in oocytes expression system","volume":"29","author":"Oda","year":"2018","journal-title":"Neuroreport"},{"issue":"2","key":"2025020410355345400_bqaf013-B29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuron.2006.03.042","article-title":"TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction","volume":"50","author":"Kwan","year":"2006","journal-title":"Neuron"},{"issue":"6","key":"2025020410355345400_bqaf013-B30","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.cell.2006.02.023","article-title":"TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents","volume":"124","author":"Bautista","year":"2006","journal-title":"Cell"},{"issue":"12","key":"2025020410355345400_bqaf013-B31","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1152\/japplphysiol.00043.2015","article-title":"Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons","volume":"118","author":"Hsu","year":"2015","journal-title":"J Appl Physiol (1985)"},{"issue":"6","key":"2025020410355345400_bqaf013-B32","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","article-title":"Calcium signaling","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"issue":"8","key":"2025020410355345400_bqaf013-B33","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0962-8924(00)01800-6","article-title":"Calmodulin: a prototypical calcium sensor","volume":"10","author":"Chin","year":"2000","journal-title":"Trends Cell Biol"},{"issue":"19","key":"2025020410355345400_bqaf013-B34","doi-asserted-by":"crossref","first-page":"11107","DOI":"10.1073\/pnas.95.19.11107","article-title":"Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases","volume":"95","author":"Sengupta","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1-2","key":"2025020410355345400_bqaf013-B35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0303-7207(02)00258-7","article-title":"The ubiquitin-proteasome pathway and the regulation of growth hormone receptor availability","volume":"197","author":"Strous","year":"2002","journal-title":"Mol Cell Endocrinol"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqaf013\/61638847\/bqaf013.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/166\/2\/bqaf013\/61638847\/bqaf013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/166\/2\/bqaf013\/61638847\/bqaf013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:36:17Z","timestamp":1738665377000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqaf013\/7981986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1,6]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqaf013","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2025,1,6]]},"article-number":"bqaf013"}}