{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:31:58Z","timestamp":1755221518066,"version":"3.43.0"},"reference-count":28,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"DOI":"10.13039\/501100002668","name":"Abant Izzet Baysal\n                        \u00dcniversitesi","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002668","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with diverse\n                    metabolic and hormonal manifestations. Insulin-like peptide 5 (INSL5), a\n                    gut-derived hormone of the relaxin\/insulin family, is expressed in the central\n                    nervous system, colonic and reproductive tissues, but its clinical significance\n                    in PCOS remains unclear. This study aimed to evaluate circulating INSL5 levels\n                    in PCOS and explore their associations with key hormonal and metabolic\n                    parameters. In this prospective cross-sectional study, 45 women with newly\n                    diagnosed PCOS and 35 age-matched healthy controls (18\u201335 years) were evaluated.\n                    Clinical characteristics, hormonal profiles, and metabolic markers \u2013 including\n                    serum anti-M\u00fcllerian hormone (AMH) and INSL5 \u2013 were assessed. INSL5 levels were\n                    measured using enzyme-linked immunosorbent assay (ELISA). Median serum INSL5\n                    levels did not differ significantly between PCOS and control groups (12.5 vs.\n                    15.5 ng\/ml; p=0.103). However, within the PCOS group, INSL5 was inversely\n                    correlated with body mass index, insulin, HOMA-IR, total and LDL cholesterol,\n                    triglycerides, fat mass, and free androgen index, and positively correlated with\n                    sex hormone-binding globulin (p&lt;0.05 for all). AMH was significantly higher\n                    in the PCOS group and demonstrated a diagnostic cut-off of 5.04 ng\/ml (AUC:\n                    0.808; sensitivity: 75.6%; specificity: 74.3%). Although INSL5 did not show\n                    diagnostic utility for PCOS, its consistent associations with insulin\n                    resistance, androgenic activity, and lipid metabolism suggest a potential role\n                    in metabolic regulation. These findings support its relevance as a candidate\n                    marker for metabolic phenotyping and warrant further investigation into its\n                    physiological role within the PCOS spectrum.<\/jats:p>","DOI":"10.1055\/a-2636-9491","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T19:28:44Z","timestamp":1751398124000},"page":"416-422","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic and Hormonal Profile of Insulin-Like Peptide 5 (INSL5) in\n                    Polycystic Ovary Syndrome: A Prospective Analysis"],"prefix":"10.1055","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-1565","authenticated-orcid":false,"given":"Deniz","family":"Cengiz","sequence":"additional","affiliation":[{"name":"Internal Medicine, Bolu Abant \u0130zzet Baysal University,\n                    Bolu, Turkey"},{"name":"Senior Health, St George\u2019s University Hospitals NHS\n                    Foundation Trust, London, United Kingdom of Great Britain and Northern\n                    Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra Nur","family":"Ademo\u011flu Dilek\u00e7i","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolic Diseases, Bolu Abant \u0130zzet\n                    Baysal University, Bolu, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6m\u00fcr","family":"Albayrak","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Bolu Abant \u0130zzet Baysal\n                    University, Bolu, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zg\u00fcr Mehmet","family":"Yis","sequence":"additional","affiliation":[{"name":"Biochemistry, Bolu Abant \u0130zzet Baysal University, Bolu,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: a\n                    systematic review and meta-analysis","volume":"31","author":"G Bozdag","year":"2016","journal-title":"Hum Reprod"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1384233","DOI":"10.3389\/fcell.2024.1384233","article-title":"The gut microbial composition in polycystic ovary syndrome with\n                    hyperandrogenemia and its association with steroid hormones","volume":"12","author":"M Li","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"G43","DOI":"10.1093\/ejendo\/lvad096","article-title":"Recommendations from the 2023 international evidence-based guideline for the\n                    assessment and management of polycystic ovary syndrome","volume":"189","author":"H J Teede","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"100162","DOI":"10.1016\/j.endmts.2024.100162","article-title":"A review on critical appraisal and pathogenesis of polycystic ovarian\n                    syndrome","volume":"14","author":"Y A Hajam","year":"2024","journal-title":"Endocr Metab Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/01443615.2019.1587604","article-title":"AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome","volume":"39","author":"M Calzada","year":"2019","journal-title":"J Obstetr Gynaecol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1210\/jc.2013-1393","article-title":"Can anti-M\u00fcllerian hormone predict the diagnosis of polycystic ovary syndrome? A\n                    systematic review and meta-analysis of extracted data","volume":"98","author":"S Iliodromiti","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1093\/humrep\/der297","article-title":"Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values\n                    of follicle count on ultrasound and of the serum AMH level for the definition of\n                    polycystic ovaries","volume":"26","author":"D Dewailly","year":"2011","journal-title":"Hum Reprod"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"116239","DOI":"10.1016\/j.bcp.2024.116239","article-title":"Developing insulin-like peptide 5-based antagonists for the G protein-coupled\n                    receptor, RXFP4","volume":"224","author":"H Wu","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1006\/geno.1999.5899","article-title":"Identification of INSL5, a new member of the insulin superfamily","volume":"60","author":"D Conklin","year":"1999","journal-title":"Genomics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1210\/en.2012-1161","article-title":"INSL5-deficient mice display an alteration in glucose homeostasis and an\n                    impaired fertility","volume":"153","author":"O Burnicka-Turek","year":"2012","journal-title":"Endocrinology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40618-018-0917-x","article-title":"Circulating insulin-like peptide 5 levels and its association with metabolic and\n                    hormonal parameters in women with polycystic ovary syndrome","volume":"42","author":"M Bicer","year":"2019","journal-title":"J Endocrinol Invest"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13048-022-01052-7","article-title":"Insulin-like peptide 5 (INSL5) positively correlates with anti-M\u00fcllerian hormone\n                    (AMH) in women with the polycystic ovary syndrome: a case-control study","volume":"15","author":"Y Chen","year":"2022","journal-title":"J Ovarian Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related\n                    to polycystic ovary syndrome","volume":"81","author":"Group A-SPCW","year":"2004","journal-title":"Fertil Steril"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1042\/BJ20141113","article-title":"The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo","volume":"466","author":"X Luo","year":"2015","journal-title":"Biochem J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.molmet.2016.01.007","article-title":"Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic\n                    glucose production","volume":"5","author":"Y S Lee","year":"2016","journal-title":"Mol Metab"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molmet.2018.07.011","article-title":"Co-storage and release of insulin-like peptide-5, glucagon-like peptide-1 and\n                    peptideYY from murine and human colonic enteroendocrine cells","volume":"16","author":"L J Billing","year":"2018","journal-title":"Mol Metab"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"11133","DOI":"10.1073\/pnas.1411413111","article-title":"Insulin-like peptide 5 is an orexigenic gastrointestinal hormone","volume":"111","author":"J Grosse","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1530\/JME-17-0152","article-title":"INSL5 activates multiple signalling pathways and regulates GLP-1 secretion in\n                    NCI-H716 cells","volume":"60","author":"S Y Ang","year":"2018","journal-title":"J Mol Endocrinol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/bph.13522","article-title":"Signal transduction pathways activated by insulin-like peptide 5 at the relaxin\n                    family peptide RXFP4 receptor","volume":"174","author":"S Y Ang","year":"2017","journal-title":"Br J Pharmacol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"170116","DOI":"10.1016\/j.peptides.2019.170116","article-title":"Insulin-like peptide 5 fails to improve metabolism or body weight in obese\n                    mice","volume":"120","author":"A N Zaykov","year":"2019","journal-title":"Peptides"},{"key":"ref22","first-page":"R45","article-title":"Reviewing the physiological roles of the novel hormone-receptor pair\n                    INSL5-RXFP4: a protective energy sensor?","volume":"69","author":"D Hechter","year":"2022","journal-title":"J Mol Endocrinol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.3390\/jcm12113752","article-title":"Body weight reduction by bariatric surgery reduces the plasma levels of the\n                    novel orexigenic gut hormone insulin-like peptide 5 in patients with severe\n                    obesity","volume":"12","author":"A Di Vincenzo","year":"2023","journal-title":"J Clin Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1055\/s-0042-109869","article-title":"Insulin-like peptide 5 interacts with sex hormones and metabolic parameters in a\n                    gender and adiposity dependent manner in humans","volume":"48","author":"I Wagner","year":"2016","journal-title":"Horm Metab Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"108493","DOI":"10.1016\/j.jdiacomp.2023.108493","article-title":"Insulin-like peptide 5 is associated with insulin resistance in women with\n                    polycystic ovary syndrome","volume":"37","author":"Y Chen","year":"2023","journal-title":"J Diabetes Complicat"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/humupd\/dmy029","article-title":"Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive\n                    physiology","volume":"24","author":"R Ivell","year":"2018","journal-title":"Hum Reprod Update"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"E1575","DOI":"10.1210\/jc.2013-1107","article-title":"Parallel variations of insulin-like peptide 3 (INSL3) and antim\u00fcllerian hormone\n                    (AMH) in women with the polycystic ovary syndrome according to menstrual cycle\n                    pattern","volume":"98","author":"C Pelusi","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1080\/09513590.2017.1416462","article-title":"Evaluation of the correlation between insulin like factor 3, polycystic ovary\n                    syndrome, and ovarian maldescent","volume":"34","author":"E Seyam","year":"2018","journal-title":"Gynecol Endocrinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/1098-2795(200103)58:3<281::AID-MRD6>3.0.CO;2-0","article-title":"Increase in final stages of follicular atresia and premature decay of corpora\n                    lutea in Insl3-deficient mice","volume":"58","author":"K Spanel-Borowski","year":"2001","journal-title":"Mol Reprod Dev"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2636-9491.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T22:57:04Z","timestamp":1754693824000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2636-9491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":28,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2025,8,8]]},"published-print":{"date-parts":[[2025,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2636-9491","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"type":"print","value":"0018-5043"},{"type":"electronic","value":"1439-4286"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}