{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:19:51Z","timestamp":1787858391055,"version":"build-2784847793"},"reference-count":38,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Studies have shown that obesity and insulin resistance are associated with central precocious puberty (CPP) in girls. Serum fibroblast growth factor 21 (FGF21) levels are associated with obesity and insulin resistance and are also related to ovarian development, reproductive function, and gonadotropin-releasing hormone (GnRH) neuron development. The aim of this study was to investigate the levels of serum FGF21 in girls with CPP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 106 girls aged 6\u201310 years who were evaluated at the hospital\u2019s Growth and Development Clinic. The cohort comprised 55 girls diagnosed with CPP as the case group and 51 age-matched girls with normal growth and development as the control group. Data including age, age at onset of puberty or menarche, anthropometric measurements, IGF1 levels, bone age (BA), ovarian and uterine development, hormone profiles, \u03b2-Klotho levels, and FGF21 levels were collected and statistically analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bone age advancement, IGF1, \u03b2-Klotho, and FGF21 levels showed statistically significant differences between the CPP and control groups. FGF21 and \u03b2-Klotho levels were negatively associated with CPP, with areas under the ROC curve of 0.833 and 0.770, respectively. The optimal cut-off values were 156.28 pg\/mL and 7,057.18 pg\/mL for \u03b2-Klotho. In girls with CPP, the FGF21 levels were weakly positively correlated with the \u03b2-Klotho levels (r = 0.273).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared with age-matched girls without pubertal initiation, girls diagnosed with CPP had significantly lower serum levels of FGF21 and \u03b2-Klotho, suggesting that FGF21 may be involved in the regulation of pubertal onset. However, the underlying molecular mechanisms require further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-26-0320","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:30:45Z","timestamp":1786635045000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast growth factor 21 and its relationship with central precocious puberty in girls"],"prefix":"10.1530","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8857-5760","authenticated-orcid":true,"given":"Xiaojing","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hebei Medical University 1 , ,","place":["Shijiazhuang, China"]},{"name":"Department of Pediatrics, Hebei General Hospital 2 , ,","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hebei General Hospital 2 , ,","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hebei General Hospital 2 , ,","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hebei General Hospital 2 , ,","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-2622","authenticated-orcid":true,"given":"Yaying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hebei Medical University 1 , ,","place":["Shijiazhuang, China"]},{"name":"Department of Pediatrics, Hebei General Hospital 2 , ,","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026082714562312000_bib1","doi-asserted-by":"crossref","first-page":"6765","DOI":"10.3390\/ijerph17186765","article-title":"The age distribution among children seeking medical treatment for precocious puberty in Taiwan","volume":"17","author":"Su","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2026082714562312000_bib2","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2022.968511","article-title":"An increasing tendency of precocious puberty among Korean children from the perspective of COVID-19 pandemic effect","volume":"10","author":"Choi","year":"2022","journal-title":"Front Pediatr"},{"key":"2026082714562312000_bib3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1210\/endrev\/bnac020","article-title":"The congenital and acquired mechanisms implicated in the etiology of central precocious puberty","volume":"44","author":"Brito","year":"2023","journal-title":"Endocr Rev"},{"key":"2026082714562312000_bib4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/aje\/kwu113","article-title":"Age at menarche and risks of all-cause and cardiovascular death: a systematic review and meta-analysis","volume":"180","author":"Charalampopoulos","year":"2014","journal-title":"Am J Epidemiol"},{"key":"2026082714562312000_bib5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.mce.2009.09.003","article-title":"Hormones in synergy: regulation of the pituitary gonadotropin genes","volume":"314","author":"Thackray","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"2026082714562312000_bib6","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1210\/er.2018-00116","article-title":"Clinical management of congenital hypogonadotropic hypogonadism","volume":"40","author":"Young","year":"2019","journal-title":"Endocr Rev"},{"key":"2026082714562312000_bib7","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/nm.3250","article-title":"FGF21 contributes to neuroendocrine control of female reproduction","volume":"19","author":"Owen","year":"2013","journal-title":"Nat Med"},{"key":"2026082714562312000_bib8","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cmet.2017.03.005","article-title":"FGF21 regulates metabolism through adipose-dependent and -Independent mechanisms","volume":"25","author":"BonDurant","year":"2017","journal-title":"Cell Metab"},{"key":"2026082714562312000_bib9","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2016.12.004","article-title":"FGF21 is an exocrine pancreas secretagogue","volume":"25","author":"Coate","year":"2017","journal-title":"Cell Metab"},{"key":"2026082714562312000_bib10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cmet.2012.08.002","article-title":"\u03b2Klotho is required for fibroblast growth factor 21 effects on growth and metabolism","volume":"16","author":"Ding","year":"2012","journal-title":"Cell Metab"},{"key":"2026082714562312000_bib11","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.15252\/emmm.201607376","article-title":"KLB, encoding \u03b2-Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism","volume":"9","author":"Xu","year":"2017","journal-title":"EMBO Mol Med"},{"key":"2026082714562312000_bib12","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.2337\/db14-0541","article-title":"FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting","volume":"63","author":"Liang","year":"2014","journal-title":"Diabetes"},{"key":"2026082714562312000_bib13","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1016\/j.peptides.2007.10.007","article-title":"The fasting polypeptide FGF21 can enter brain from blood","volume":"28","author":"Hsuchou","year":"2007","journal-title":"Peptides"},{"key":"2026082714562312000_bib14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1530\/rep.1.00617","article-title":"Neuroendocrine control of reproductive aging: roles of GnRH neurons","volume":"131","author":"Yn","year":"2006","journal-title":"Reproduction"},{"key":"2026082714562312000_bib15","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1210\/me.2013-1413","article-title":"Minireview: metabolism of female reproduction: regulatory mechanisms and clinical implications","volume":"28","author":"Seli","year":"2014","journal-title":"Mol Endocrinol"},{"key":"2026082714562312000_bib16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3390\/nu8020087","article-title":"The deep correlation between energy metabolism and reproduction: a view on the effects of nutrition for women fertility","volume":"8","author":"Fontana","year":"2016","journal-title":"Nutrients"},{"key":"2026082714562312000_bib17","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.cmet.2013.04.005","article-title":"Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice","volume":"17","author":"Lin","year":"2013","journal-title":"Cell Metab"},{"key":"2026082714562312000_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2020.128776","article-title":"Prenatal exposure of female mice to perfluorononanoic acid delays pubertal activation of the reproductive endocrine axis through enhanced hepatic FGF21 production","volume":"269","author":"Zhang","year":"2021","journal-title":"Chemosphere"},{"key":"2026082714562312000_bib19","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuron.2025.03.012","article-title":"Feed or breed: hypothalamic mechanisms linking energy availability to puberty onset","volume":"113","author":"Sicardi","year":"2025","journal-title":"Neuron"},{"key":"2026082714562312000_bib20","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.tem.2010.05.003","article-title":"Energy balance and puberty onset: emerging role of central mTOR signaling","volume":"21","author":"Roa","year":"2010","journal-title":"Trends Endocrinol Metab"},{"key":"2026082714562312000_bib21","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/s42255-025-01236-7","article-title":"Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men","volume":"7","author":"Nicolaisen","year":"2025","journal-title":"Nat Metab"},{"key":"2026082714562312000_bib22","first-page":"16","article-title":"Expert consensus on the diagnosis and treatment of central precocious puberty(2022)","volume":"61","author":"Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association","year":"2023","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"2026082714562312000_bib23","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1210\/en.2008-0285","article-title":"Bezafibrate, a peroxisome proliferator-activated receptors agonist, decreases body temperature and enhances electroencephalogram delta-oscillation during sleep in mice","volume":"149","author":"Chikahisa","year":"2008","journal-title":"Endocrinology"},{"key":"2026082714562312000_bib24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/humupd\/dmn058","article-title":"The role of kisspeptin in the control of gonadotrophin secretion","volume":"15","author":"Roseweir","year":"2009","journal-title":"Hum Reprod Update"},{"key":"2026082714562312000_bib25","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1523\/JNEUROSCI.1775-08.2008","article-title":"Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge","volume":"28","author":"Clarkson","year":"2008","journal-title":"J Neurosci"},{"key":"2026082714562312000_bib26","doi-asserted-by":"crossref","DOI":"10.1111\/jne.12848","article-title":"Exposure of female mice to perfluorooctanoic acid suppresses hypothalamic kisspeptin-reproductive endocrine system through enhanced hepatic fibroblast growth factor 21 synthesis, leading to ovulation failure and prolonged dioestrus","volume":"32","author":"Zhang","year":"2020","journal-title":"J Neuroendocrinol"},{"key":"2026082714562312000_bib27","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1210\/me.2010-0142","article-title":"Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse","volume":"24","author":"Fon Tacer","year":"2010","journal-title":"Mol Endocrinol"},{"key":"2026082714562312000_bib28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41387-024-00335-w","article-title":"Alternate-day fasting delays pubertal development in normal-weight mice but prevents high-fat diet-induced obesity and precocious puberty","volume":"14","author":"Ullah","year":"2024","journal-title":"Nutr Diabetes"},{"key":"2026082714562312000_bib29","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0134656","article-title":"Association of obesity with onset of puberty and sex hormones in Chinese girls: a 4-year longitudinal study","volume":"10","author":"Zhai","year":"2015","journal-title":"PLoS One"},{"key":"2026082714562312000_bib30","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.195","article-title":"Time-restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21","volume":"10","author":"Hua","year":"2020","journal-title":"Clin Transl Med"},{"key":"2026082714562312000_bib31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/vms3.653","article-title":"Potential of Hibiscus sabdariffa Linn. in managing FGF21 resistance in diet-induced-obesity rats via miR-34a regulation","volume":"8","author":"Kartinah","year":"2022","journal-title":"Vet Med Sci"},{"key":"2026082714562312000_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1105602","article-title":"The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants","volume":"14","author":"Mistry","year":"2023","journal-title":"Front Endocrinol"},{"key":"2026082714562312000_bib33","doi-asserted-by":"crossref","first-page":"R486","DOI":"10.1152\/ajpregu.00316.2018","article-title":"Low-protein and methionine, high-starch diets increase energy intake and expenditure, increase FGF21, decrease IGF1, and have little effect on adiposity in mice","volume":"316","author":"Chaumontet","year":"2019","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2026082714562312000_bib34","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1210\/jc.2012-1221","article-title":"Fibroblast growth factor 21 (FGF-21) and its relation to obesity, metabolic syndrome, and nonalcoholic fatty liver in children: a longitudinal analysis","volume":"97","author":"Reinehr","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082714562312000_bib35","first-page":"354","article-title":"Fibroblast growth factor 21: effects on carbohydrate and lipid metabolism in health and disease","volume":"14","author":"Kralisch","year":"2011","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"2026082714562312000_bib36","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1273170","article-title":"The value of luteinizing hormone basal values and sex hormone-binding globulin for early diagnosis of rapidly progressive central precocious puberty","volume":"14","author":"Zhang","year":"2024","journal-title":"Front Endocrinol"},{"key":"2026082714562312000_bib37","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0026-0495(90)90309-Z","article-title":"Regulation of sex hormone-binding globulin production by growth factors","volume":"39","author":"Plymate","year":"1990","journal-title":"Metabolism"},{"key":"2026082714562312000_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1298374","article-title":"An updated meta-analysis of the relationship between vitamin D levels and precocious puberty","volume":"14","author":"Cheng","year":"2023","journal-title":"Front Endocrinol"}],"container-title":["Endocrine Connections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0320\/523546\/ec-26-0320.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0320\/523546\/ec-26-0320.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:56:32Z","timestamp":1787856992000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article\/15\/8\/e260320\/77993\/Fibroblast-growth-factor-21-and-its-relationship"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":38,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/ec-26-0320","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]},"article-number":"e260320"}}