{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:14:46Z","timestamp":1791000886172,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1003703"],"award-info":[{"award-number":["2018YFC1003703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771611"],"award-info":[{"award-number":["81771611"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant\u2013like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.<\/jats:p>","DOI":"10.3390\/biom11060857","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T04:22:22Z","timestamp":1623212542000},"page":"857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis"],"prefix":"10.3390","volume":"11","author":[{"given":"Rongrong","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Biotechnology College of Veterinary Medicine, Northwest A&F University, Ministry of Agriculture, Yangling 712100, China"},{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xiong","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xue","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baobei","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxia","family":"Xiao","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-9008","authenticated-orcid":false,"given":"Xiaohua","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biotechnology College of Veterinary Medicine, Northwest A&F University, Ministry of Agriculture, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","first-page":"189","article-title":"Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression","volume":"91","author":"Wal","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.4088\/JCP.14m09298","article-title":"The economic burden of adults with major depressive disorder in the United States (2005 and 2010)","volume":"76","author":"Greenberg","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/09513599309152489","article-title":"Liver metabolism during treatment with estradiol and natural progesterone","volume":"7","author":"Darj","year":"1993","journal-title":"Gynecol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1210\/endo-118-4-1445","article-title":"Ontogeny of the stress response in the rat: Role of the pituitary and the hypothalamus","volume":"118","author":"Walker","year":"1986","journal-title":"Endocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/nn.4112","article-title":"Sex differences and stress across the lifespan","volume":"18","author":"Bale","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11920-017-0834-2","article-title":"Depression and Anxiety in Polycystic Ovary Syndrome: Etiology and Treatment","volume":"19","author":"Cooney","year":"2017","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1093\/humrep\/dex044","article-title":"High prevalence of moderate and severe depressive and anxiety symptoms in polycystic ovary syndrome: A systematic review and meta-analysis","volume":"32","author":"Cooney","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.steroids.2011.12.008","article-title":"Mood and anxiety disorders in women with PCOS","volume":"77","author":"Dokras","year":"2012","journal-title":"Steroids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0015-0282(01)02008-8","article-title":"A prospective study of stress among women undergoing in vitro fertilization or gamete intrafallopian transfer","volume":"76","author":"Chu","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10815-012-9904-x","article-title":"Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilization treatment: Psychological and neurohormonal assessment","volume":"30","author":"An","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4314\/ahs.v16i2.12","article-title":"The effect of anxiety and depression scores of couples who underwent assisted reproductive techniques on the pregnancy outcomes","volume":"16","author":"Terzioglu","year":"2016","journal-title":"Afr. Health Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/13548506.2016.1218031","article-title":"The effects of anxiety and depression on in vitro fertilisation outcomes of infertile Chinese women","volume":"22","author":"Xu","year":"2017","journal-title":"Psychol. Health Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.31887\/DCNS.2018.20.1\/klrooney","article-title":"The relationship between stress and infertility","volume":"20","author":"Rooney","year":"2018","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.cytogfr.2011.11.004","article-title":"Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism","volume":"22","author":"Bondue","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1006\/geno.1994.1549","article-title":"Cloning of human genes encoding novel G protein-coupled receptors","volume":"23","author":"Marchese","year":"1994","journal-title":"Genomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.1128\/JVI.73.6.5231-5239.1999","article-title":"An Orphan G Protein-Coupled Receptor, GPR1, Acts as a Coreceptor To Allow Replication of Human Immunodeficiency Virus Types 1 and 2 in Brain-Derived Cells","volume":"73","author":"Nobuaki","year":"1999","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1530\/JOE-15-0521","article-title":"The role of GPR1 signaling in mice corpus luteum","volume":"230","author":"Yang","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.omto.2020.08.013","article-title":"A Screened GPR1 Peptide Exerts Antitumor Effects on Triple-Negative Breast Cancer","volume":"18","author":"Huang","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/1742-2094-8-100","article-title":"Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy","volume":"8","author":"Kang","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/ijnp\/pyy005","article-title":"The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice","volume":"21","author":"Jing","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00442247","article-title":"Discovery of antidepressant activity by forced swimming test may depend on pre-exposure of rats to a stressful situation","volume":"97","author":"Borsini","year":"1989","journal-title":"Psychopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-2094-5-15","article-title":"Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia","volume":"5","author":"Henry","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejphar.2014.09.049","article-title":"Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice","volume":"744","author":"Sulakhiya","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cell.2008.08.040","article-title":"Anatomical profiling of G protein-coupled receptor expression","volume":"135","author":"Regard","year":"2008","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5114\/ceji.2015.49427","article-title":"The effects of EGb761 on lipopolysaccharide-induced depressive-like behaviour in C57BL\/6J mice","volume":"40","author":"Zhao","year":"2015","journal-title":"Cent. Eur J. Immunol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbr.2004.04.008","article-title":"Strain differences in sucrose preference and in the consequences of unpredictable chronic mild stress","volume":"155","author":"Pothion","year":"2004","journal-title":"Behav. Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/BF00187257","article-title":"Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant","volume":"93","author":"Willner","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.pbb.2006.06.005","article-title":"Animal models of depression in drug discovery: A historical perspective","volume":"84","author":"Mcarthur","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1037\/a0035302","article-title":"From stress to inflammation and major depressive disorder: A social signal transduction theory of depression","volume":"140","author":"Slavich","year":"2014","journal-title":"Psychol. Bull."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/sj.npp.1301488","article-title":"Intranasal immune challenge induces sex-dependent depressive-like behavior and cytokine expression in the brain","volume":"33","author":"Tonelli","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1742-2094-11-41","article-title":"Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy","volume":"11","author":"Xie","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_32","first-page":"1998","article-title":"Effects of Combination Therapy of Dexamethasone and Fluoxetine on Levels of Interleukin-1 beta and Interleukin-6 in a Rat Model of Asthma with Depressive-like Behaviors","volume":"6","author":"Li","year":"2012","journal-title":"HealthMED"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.12740\/PP\/37705","article-title":"BDNF as a biomarker in the course and treatment of schizophrenia","volume":"49","author":"Drozdowicz","year":"2015","journal-title":"Psychiatr. Pol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"De Kloet, E.R., Otte, C., Kumsta, R., Kok, L., Hillegers, M.H., Hasselmann, H., Kliegel, D., and Jo\u00ebls, M. (2016). Stress and Depression: A Crucial Role of the Mineralocorticoid Receptor. J. Neuroendocrinol., 28.","DOI":"10.1111\/jne.12379"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuropharm.2015.10.034","article-title":"BDNF\u2014A key transducer of antidepressant effects","volume":"102","author":"Monteggia","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2174\/1570159X14666160119094646","article-title":"Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets","volume":"14","author":"Zhang","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00213-016-4483-7","article-title":"Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation","volume":"234","author":"Ma","year":"2017","journal-title":"Psychopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1001\/archpsyc.60.8.804","article-title":"Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects","volume":"60","author":"Dwivedi","year":"2003","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bcp.2017.05.019","article-title":"Sex steroids and neurogenesis","volume":"141","author":"Heberden","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.psyneuen.2016.01.013","article-title":"Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice","volume":"66","author":"Zhang","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1095\/biolreprod35.1.27","article-title":"Synergism between granulosa and theca-interstitial cells in estrogen biosynthesis by gonadotropin-treated rat ovaries: Studies on the two-cell, two-gonadotropin hypothesis using steroid antisera","volume":"35","author":"Liu","year":"1986","journal-title":"Biol. Reprod."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:12:17Z","timestamp":1760163137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,9]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["biom11060857"],"URL":"https:\/\/doi.org\/10.3390\/biom11060857","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,9]]}}}