{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:42Z","timestamp":1791908262886,"version":"4.3.4"},"reference-count":185,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Metabolic syndrome (MetS) is a cluster of conditions, including obesity, insulin resistance (IR), dyslipidemia, and hypertension, that increase the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). While studied often in adults, the increasing prevalence of MetS in children and adolescents underscores the need for its early detection and intervention. Among various biomarkers, sex hormone-binding globulin (SHBG) has gained substantial attention due to its associations with metabolic health and disease. This review provides a comprehensive overview of SHBG and its association with MetS, with a focus on the pediatric and adolescent population. The interplay between SHBG, puberty, and metabolic risk factors is explored, including racial and ethnic variations. SHBG plays a crucial role in transporting sex hormones and regulating their bioavailability and has been found to correlate inversely with obesity and IR, two key components of MetS. Puberty represents a critical period during which hormonal changes and metabolic shifts may further influence SHBG levels and metabolic health. Understanding SHBG\u2019s role in early metabolic risk detection could provide novel insights into the prevention and management of MetS.<\/jats:p>","DOI":"10.3390\/metabo15080494","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:42Z","timestamp":1753196442000},"page":"494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty"],"prefix":"10.3390","volume":"15","author":[{"given":"Banu","family":"Aydin","sequence":"first","affiliation":[{"name":"Department of Medical Cell Biology, Uppsala University, 751 23 Uppsala, Sweden"},{"name":"Department of Women\u2019s and Children\u2019s Health, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Winters","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1056\/NEJMoa031049","article-title":"Obesity and the metabolic syndrome in children and adolescents","volume":"350","author":"Weiss","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jpeds.2007.09.010","article-title":"Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later","volume":"152","author":"Morrison","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4274\/jcrpe.2764","article-title":"Sex Hormone-Binding Globulin in Children and Adolescents","volume":"8","author":"Winters","year":"2016","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0960-0760(91)90307-Q","article-title":"Sex hormone-binding globulin: Anatomy and physiology of a new regulatory system","volume":"40","author":"Rosner","year":"1991","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-16-0070","article-title":"Plasma steroid-binding proteins: Primary gatekeepers of steroid hormone action","volume":"230","author":"Hammond","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1210\/jcem-53-1-58","article-title":"Transport of steroid hormones: Binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma","volume":"53","author":"Dunn","year":"1981","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","first-page":"3979","article-title":"Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone\u2013binding globulin gene","volume":"117","author":"Selva","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"668","DOI":"10.4158\/EP12026.OR","article-title":"Sex Hormone-Binding Globulin and The Risk for Metabolic Syndrome in Children of South Asian Indian Origin","volume":"18","author":"Krishnasamy","year":"2012","journal-title":"Endocr. Pract."},{"key":"ref_9","first-page":"188","article-title":"Sex hormone-binding globulin levels and metabolic syndrome and its features in adolescents","volume":"11","author":"Schoppen","year":"2010","journal-title":"Pediatr. Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Urbano, F., Chiarito, M., Lattanzio, C., Messa, A., Ferrante, M., Francavilla, M., Mehmeti, I., Lassandro, G., Giordano, P., and Faienza, M.F. (2022). Sex Hormone-Binding Globulin (SHBG) Reduction: The Alarm Bell for the Risk of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome. Children, 9.","DOI":"10.3390\/children9111748"},{"key":"ref_11","first-page":"545","article-title":"Sex Hormone-Binding Globulin Reduction in Metabolic Disorders May Play a Role in NAFLD Development","volume":"158","author":"Hernandez","year":"2017","journal-title":"Endocrinology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12906","DOI":"10.1111\/ijpo.12906","article-title":"High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition","volume":"17","author":"Aydin","year":"2022","journal-title":"Pediatr. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S1054-139X(02)00485-8","article-title":"Growth at puberty","volume":"31","author":"Rogol","year":"2002","journal-title":"J. Adolesc. Health Off. Publ. Soc. Adolesc. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/EJE-08-0878","article-title":"Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects","volume":"160","author":"Brufani","year":"2009","journal-title":"Eur. J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1196\/annals.1429.009","article-title":"Adolescent obesity and puberty: The \u201cperfect storm\u201d","volume":"1135","author":"Jasik","year":"2008","journal-title":"Ann N Y Acad Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/0014-5793(87)80121-7","article-title":"The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain","volume":"215","author":"Hammond","year":"1987","journal-title":"FEBS Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25920","DOI":"10.1074\/jbc.M004484200","article-title":"Steroid-binding specificity of human sex hormone-binding globulin is influenced by occupancy of a zinc-binding site","volume":"275","author":"Avvakumov","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0083-6729(08)61148-6","article-title":"Structure, function, and regulation of androgen-binding protein\/sex hormone-binding globulin","volume":"49","author":"Joseph","year":"1994","journal-title":"Vitam. Horm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1055\/s-2006-925336","article-title":"Human sex hormone-binding globulin is expressed in testicular germ cells and not in sertoli cells","volume":"38","author":"Selva","year":"2006","journal-title":"Horm. Metab. Res. Horm. Stoffwechselforschung Horm. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nakhla, A.M., Hryb, D.J., Rosner, W., Romas, N.A., Xiang, Z., and Kahn, S.M. (2009). Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing. BMC Mol. Biol., 10.","DOI":"10.1186\/1471-2199-10-37"},{"key":"ref_21","first-page":"1821","article-title":"Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males","volume":"81","author":"Vermeulen","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40842-020-00106-3","article-title":"SHBG and total testosterone levels in men with adult onset hypogonadism: What are we overlooking?","volume":"6","author":"Winters","year":"2020","journal-title":"Clin. Diabetes Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1365-2265.2005.02252.x","article-title":"Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower levels of non-SHBG-bound testosterone in male newborns and healthy adult men","volume":"62","author":"Pierik","year":"2005","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000184787","article-title":"Sex hormone-binding globulin: Gene organization and structure\/function analyses","volume":"45","author":"Hammond","year":"1996","journal-title":"Horm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1172\/JCI0214060","article-title":"Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction","volume":"109","author":"Hogeveen","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E1798","DOI":"10.1210\/jc.2014-2055","article-title":"Sex hormone binding globulin deficiency due to a homozygous missense mutation","volume":"99","author":"Vos","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"bvab125","DOI":"10.1210\/jendso\/bvab125","article-title":"Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl","volume":"5","author":"Andriessen","year":"2021","journal-title":"J. Endocr. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ohlsson, C., Wallaschofski, H., Lunetta, K.L., Stolk, L., Perry, J.R.B., Koster, A., Petersen, A.K., Eriksson, J., Lehtim\u00e4ki, T., and Huhtaniemi, I.T. (2011). Genetic determinants of serum testosterone concentrations in men. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002313"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1210\/me.2014-1058","article-title":"Naturally occurring mutants inform SHBG structure and function","volume":"28","author":"Wu","year":"2014","journal-title":"Mol. Endocrinol. Baltim. Md."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e641","DOI":"10.1210\/clinem\/dgae280","article-title":"SHBG Gene Polymorphisms and Their Influence on Serum SHBG, Total and Free Testosterone Concentrations in Men","volume":"110","author":"Walravens","year":"2025","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","first-page":"1066","article-title":"Molecular analyses of a human sex hormone-binding globulin variant: Evidence for an additional carbohydrate chain","volume":"75","author":"Power","year":"1992","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","first-page":"235","article-title":"Human variant sex hormone-binding globulin (SHBG) with an additional carbohydrate chain has a reduced clearance rate in rabbit","volume":"83","author":"Cousin","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1056\/NEJMoa0804381","article-title":"Sex hormone-binding globulin and risk of type 2 diabetes in women and men","volume":"361","author":"Ding","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/hmg\/ddp522","article-title":"Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes","volume":"19","author":"Perry","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1210\/jc.2006-0679","article-title":"SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density","volume":"91","author":"Eriksson","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.2047-2927.2013.00174.x","article-title":"Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: The Troms\u00f8 Study","volume":"2","author":"Svartberg","year":"2014","journal-title":"Andrology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.2337\/db23-0982","article-title":"Association Between Low Sex Hormone-Binding Globulin and Increased Risk of Type 2 Diabetes Is Mediated by Increased Visceral and Liver Fat: Results from Observational and Mendelian Randomization Analyses","volume":"73","author":"Stangl","year":"2024","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"White, M.J., Eren, F., Agirbasli, D., Williams, S.M., and Agirbasli, M. (2015). SHBG gene polymorphism (rs1799941) associates with metabolic syndrome in children and adolescents. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116915"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36383","DOI":"10.1074\/jbc.M104681200","article-title":"Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence","volume":"276","author":"Hogeveen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1365-2265.2008.03365.x","article-title":"Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men","volume":"70","author":"Vanbillemont","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.rbmo.2020.10.003","article-title":"Association between human SHBG gene polymorphisms and risk of PCOS: A meta-analysis","volume":"42","author":"Li","year":"2021","journal-title":"Reprod. Biomed. Online"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0960-0760(93)90104-5","article-title":"Evidence that human placenta is a site of sex hormone-binding globulin gene expression","volume":"46","author":"Larrea","year":"1993","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1080\/09513590903015437","article-title":"The change in sex hormone binding globulin and the influence by gestational diabetes mellitus in fetal period","volume":"25","author":"Jin","year":"2009","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jsbmb.2017.03.022","article-title":"Umbilical cord blood androgen levels in girls and boys assessed by gas chromatography-tandem mass spectrometry","volume":"171","author":"Lundell","year":"2017","journal-title":"J Steroid Biochem. Mol. Biol."},{"key":"ref_45","first-page":"335","article-title":"Impact of Smoking, Obesity and Maternal Diabetes on SHBG Levels in Newborns","volume":"130","author":"Aydin","year":"2022","journal-title":"Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2265.1989.tb01243.x","article-title":"Circulating sex hormone-binding globulin and testosterone in newborns and infants","volume":"31","author":"Bolton","year":"1989","journal-title":"Clin. Endocrinol."},{"key":"ref_47","first-page":"625","article-title":"Reference intervals for testosterone, androstenedione and SHBG levels in healthy females and males from birth until old age","volume":"51","author":"Elmlinger","year":"2005","journal-title":"Clin. Lab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"bvae179","DOI":"10.1210\/jendso\/bvae179","article-title":"Postnatal Dysregulation of Androgens in Extremely Preterm Male Infants","volume":"8","author":"Nilsson","year":"2024","journal-title":"J. Endocr. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1210\/jcem-71-5-1147","article-title":"Thyroid hormones influences sex steroid binding protein levels in infancy: Study in congenital hypothyroidism","volume":"71","author":"Leger","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1203\/00006450-198612000-00028","article-title":"Transient increase in postnatal testicular activity is not revealed by longitudinal measurements of salivary testosterone","volume":"20","author":"Huhtaniemi","year":"1986","journal-title":"Pediatr. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000454862","article-title":"Salivary Testosterone during the Minipuberty of Infancy","volume":"87","author":"Contreras","year":"2017","journal-title":"Horm. Res. Paediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1210\/clinem\/dgac155","article-title":"Reference Curves for Pediatric Endocrinology: Leveraging Biomarker Z-Scores for Clinical Classifications","volume":"107","author":"Madsen","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1210\/jc.2013-3902","article-title":"Adiposity, chronic inflammation, and the prepubertal decline of sex hormone binding globulin in children: Evidence for associations with the timing of puberty (Earlybird 58)","volume":"99","author":"Pinkney","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1177\/0004563215610589","article-title":"Estimating age-specific trends in circulating testosterone and sex hormone-binding globulin in males and females across the lifespan","volume":"53","author":"Handelsman","year":"2016","journal-title":"Ann. Clin. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.metabol.2009.06.033","article-title":"Sex hormone-binding globulin and lipid profile in pubertal children","volume":"59","author":"Cano","year":"2010","journal-title":"Metabolism"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1210\/jcem-65-6-1107","article-title":"High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: Effect of recombinant human growth hormone treatment","volume":"65","author":"Belgorosky","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1210\/jcem-58-5-915","article-title":"Plasma sex hormone-binding globulin levels decrease during the second decade of life irrespective of pubertal status","volume":"58","author":"Cunningham","year":"1984","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_58","first-page":"2832","article-title":"A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition","volume":"85","author":"Burger","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e13866","DOI":"10.1111\/eci.13866","article-title":"Sex steroids and sex steroid-binding globulin levels amongst middle-aged and elderly men and women from general population","volume":"52","author":"Aribas","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e3946","DOI":"10.1210\/clinem\/dgab416","article-title":"Definition, Prevalence, and Risk Factors of Low Sex Hormone-Binding Globulin in US Adults","volume":"106","author":"Wang","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0015-0282(16)53212-9","article-title":"Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women","volume":"53","author":"Murphy","year":"1990","journal-title":"Fertil. Steril."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1089\/jwh.2011.2839","article-title":"Are all estrogens created equal? A review of oral vs. transdermal therapy","volume":"21","author":"Goodman","year":"2012","journal-title":"J. Womens Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"E2780","DOI":"10.1210\/jc.2014-2640","article-title":"Sex hormone-binding globulin gene expression and insulin resistance","volume":"99","author":"Winters","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1046\/j.1365-2265.1997.2551065.x","article-title":"Serum LH concentrations in hypogonadal men during transdermal testosterone replacement through scrotal skin: Further evidence that ageing enhances testosterone negative feedback. The Testoderm Study Group","volume":"47","author":"Winters","year":"1997","journal-title":"Clin. Endocrinol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1080\/00365513.2017.1286685","article-title":"Circulating androgens and SHBG during the normal menstrual cycle in two ethnic populations","volume":"77","author":"Rezaii","year":"2017","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/clinchem\/37.5.667","article-title":"Longitudinal assessment of changes in reproductive hormones during normal pregnancy","volume":"37","author":"Boyne","year":"1991","journal-title":"Clin. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1210\/jc.2007-1972","article-title":"Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study","volume":"93","author":"Wu","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E1695","DOI":"10.1210\/jc.2012-1614","article-title":"Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? Results from the Study of Women\u2019s Health Across the Nation","volume":"97","author":"Wildman","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1210\/clinem\/dgab470","article-title":"Aging, Cardiovascular Risk, and SHBG Levels in Men and Women From the General Population","volume":"106","author":"Aribas","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.1515\/cclm-2015-0027","article-title":"Pediatric reference intervals for calculated free testosterone, bioavailable testosterone and free androgen index in the CALIPER cohort","volume":"53","author":"Raizman","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.euf.2017.05.007","article-title":"Serum Concentrations of Sex Hormone-binding Globulin Vary Widely in Younger and Older Men: Clinical Data from a Men\u2019s Health Practice","volume":"5","author":"Krakowsky","year":"2019","journal-title":"Eur. Urol. Focus"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1210\/jc.2002-020557","article-title":"The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: Implications for SHBG as a surrogate marker of insulin resistance","volume":"88","author":"Jayagopal","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"909","DOI":"10.2337\/dc08-1618","article-title":"Sex Hormone\u2013Binding Globulin Levels Predict Insulin Sensitivity, Disposition Index, and Cardiovascular Risk During Puberty","volume":"32","author":"Aksglaede","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1093\/humrep\/dem145","article-title":"Heritability of reproductive hormones in adult male twins","volume":"22","author":"Kuijper","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/0026-0495(86)90020-X","article-title":"Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins","volume":"35","author":"Meikle","year":"1986","journal-title":"Metabolism"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Coviello, A.D., Haring, R., Wellons, M., Vaidya, D., Lehtim\u00e4ki, T., Keildson, S., Lunetta, K.L., He, C., Fornage, M., and Lagou, V. (2012). A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002805"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41591-020-0751-5","article-title":"Using human genetics to understand the disease impacts of testosterone in men and women","volume":"26","author":"Ruth","year":"2020","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1210\/clinem\/dgae104","article-title":"Polygenic Scores for Adult Testosterone and SHBG Levels Are Associated with Reproductive Hormone Levels in Male Infants","volume":"109","author":"Busch","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1447-0756.2012.01919.x","article-title":"Intrauterine insulin resistance in fetuses of overweight mothers","volume":"39","author":"Liu","year":"2013","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1111\/1440-1681.13712","article-title":"\u03b2-Carotene regulates glucose transport and insulin resistance in gestational diabetes mellitus by increasing the expression of SHBG","volume":"49","author":"Liu","year":"2022","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hanem, L.G.E., Salvesen, \u00d8., Madsen, A., Sagen, J.V., Mellgren, G., Juliusson, P.B., Carlsen, S.M., Vanky, E., and \u00d8deg\u00e5rd, R. (2021). Maternal PCOS status and metformin in pregnancy: Steroid hormones in 5-10 years old children from the PregMet randomized controlled study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0257186"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.metabol.2009.03.024","article-title":"Sex hormones and metabolic syndrome in children and adolescents","volume":"58","author":"Agirbasli","year":"2009","journal-title":"Metabolism"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1210\/jcem-45-6-1211","article-title":"Low serum testosterone and sex-hormone-binding-globulin in massively obese men","volume":"45","author":"Glass","year":"1977","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"La Vignera, S., Condorelli, R.A., Calogero, A.E., Cannarella, R., and Aversa, A. (2023). Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020672"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/S0015-0282(16)56632-1","article-title":"Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women","volume":"61","author":"Guzick","year":"1994","journal-title":"Fertil. Steril."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1530\/EJE-07-0893","article-title":"Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: The Health in Men Study","volume":"158","author":"Chubb","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1210\/jc.2006-2764","article-title":"Aging, androgens, and the metabolic syndrome in a longitudinal study of aging","volume":"92","author":"Rodriguez","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0026-0495(03)00066-0","article-title":"Relationship between sex hormone-binding globulin levels and features of the metabolic syndrome","volume":"52","author":"Hajamor","year":"2003","journal-title":"Metabolism"},{"key":"ref_89","first-page":"63","article-title":"Correlation between Hormonal Statuses and Metabolic Syndrome in Postmenopausal Women","volume":"7","author":"Ziaei","year":"2013","journal-title":"J. Fam. Reprod. Health"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/j.1365-2605.2011.01230.x","article-title":"Trends in sex hormone concentrations in U.S. males: 1988\u20131991 to 1999\u20132004","volume":"35","author":"Nyante","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.metabol.2004.07.018","article-title":"Racial difference in circulating sex hormone-binding globulin levels in prepubertal boys","volume":"54","author":"Abdelrahaman","year":"2005","journal-title":"Metabolism"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"bvab008","DOI":"10.1210\/jendso\/bvab008","article-title":"Racial and Ethnic Differences in Metabolic Disease in Adolescents with Obesity and Polycystic Ovary Syndrome","volume":"5","author":"Andrisse","year":"2021","journal-title":"J Endocr Soc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/dme.12225","article-title":"Racial\/ethnic differences in hepatic steatosis in a population-based cohort of post-menopausal women: The Michigan Study of Women\u2019s Health Across the Nation","volume":"30","author":"Kim","year":"2013","journal-title":"Diabet. Med. J. Br. Diabet. Assoc."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1161\/01.CIR.0000157697.54255.CE","article-title":"Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN)","volume":"111","author":"Wildman","year":"2005","journal-title":"Circulation"},{"key":"ref_95","first-page":"2147","article-title":"Racial differences in premenopausal endogenous hormones","volume":"14","author":"Pinheiro","year":"2005","journal-title":"Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"ref_96","first-page":"817","article-title":"Racial\/ethnic differences in serum sex steroid hormone concentrations in US adolescent males","volume":"24","author":"Lopez","year":"2013","journal-title":"Cancer Causes Control CCC"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1093\/oxfordjournals.aje.a008832","article-title":"Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial","volume":"143","author":"Haffner","year":"1996","journal-title":"Am. J. Epidemiol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Engmann, L., Jin, S., Sun, F., Legro, R.S., Polotsky, A.J., Hansen, K.R., Coutifaris, C., Diamond, M.P., Eisenberg, E., and Zhang, H. (2017). Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype. Am. J. Obstet. Gynecol., 216.","DOI":"10.1016\/j.ajog.2017.01.003"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1055\/s-2005-865807","article-title":"Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups","volume":"113","author":"Heald","year":"2005","journal-title":"Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1046\/j.1365-2265.2002.01603.x","article-title":"Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: Is there a difference?","volume":"57","author":"Wijeyaratne","year":"2002","journal-title":"Clin. Endocrinol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/dme.12642","article-title":"Endogenous sex steroid hormones and glucose in a South-Asian population without diabetes: The Metabolic Syndrome and Atherosclerosis in South-Asians Living in America pilot study","volume":"32","author":"Needham","year":"2015","journal-title":"Diabet. Med. J. Br. Diabet. Assoc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.1210\/jc.2006-0037","article-title":"Serum androgen levels in black, Hispanic, and white men","volume":"91","author":"Litman","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_103","first-page":"275","article-title":"Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes","volume":"76","author":"Birkeland","year":"1993","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/cen.12086","article-title":"Sex hormone binding globulin and insulin resistance","volume":"78","author":"Wallace","year":"2013","journal-title":"Clin. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0960-0760(91)90310-2","article-title":"Pathophysiology of sex hormone binding globulin (SHBG): Relation to insulin","volume":"40","author":"Pugeat","year":"1991","journal-title":"J Steroid Biochem. Mol. Biol."},{"key":"ref_106","first-page":"85","article-title":"Sex hormone-binding globulin as a marker for hyperinsulinemia and\/or insulin resistance in obese children","volume":"143","author":"Valle","year":"2000","journal-title":"Eur. J. Endocrinol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1136\/adc.85.6.489","article-title":"Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity","volume":"85","author":"Galloway","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0960-0760(92)90081-S","article-title":"Steroidal and non-steroidal factors in plasma sex hormone binding globulin regulation","volume":"43","author":"Toscano","year":"1992","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_109","first-page":"2515","article-title":"Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male noninsulin-dependent diabetes mellitus patients","volume":"81","author":"Katsuki","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.ijo.0800351","article-title":"Achievement of near-normal body weight as the prerequisite to normalize sex hormone-binding globulin concentrations in massively obese men","volume":"21","author":"Pasquali","year":"1997","journal-title":"Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Study Obes."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.metabol.2012.12.004","article-title":"Resistance training increases SHBG in overweight\/obese, young men","volume":"62","author":"Roberts","year":"2013","journal-title":"Metabolism"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1210\/jcem-72-1-83","article-title":"A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome","volume":"72","author":"Nestler","year":"1991","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_113","first-page":"160","article-title":"Regulation of production and secretion of sex hormone-binding globulin in HepG2 cell cultures by hormones and growth factors","volume":"80","author":"Loukovaara","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1210\/jcem-67-3-460","article-title":"Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin","volume":"67","author":"Plymate","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1210\/en.2008-1289","article-title":"Peroxisome-proliferator receptor gamma represses hepatic sex hormone-binding globulin expression","volume":"150","author":"Selva","year":"2009","journal-title":"Endocrinology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.2337\/dc07-2169","article-title":"Sex hormone-binding globulin and testosterone in individuals with childhood diabetes","volume":"31","author":"Danielson","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3132\/dvdr.2008.022","article-title":"Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes","volume":"5","author":"Kapoor","year":"2008","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1182\/blood-2016-12-755967","article-title":"The hepatocyte-specific HNF4\u03b1\/miR-122 pathway contributes to iron overload-mediated hepatic inflammation","volume":"130","author":"Li","year":"2017","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.apsb.2016.07.003","article-title":"Crosstalk of HNF4\u03b1 with extracellular and intracellular signaling pathways in the regulation of hepatic metabolism of drugs and lipids","volume":"6","author":"Lu","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Baciu, C., Pasini, E., Angeli, M., Schwenger, K., Afrin, J., Humar, A., Fischer, S., Patel, K., Allard, J., and Bhat, M. (2017). Systematic integrative analysis of gene expression identifies HNF4A as the central gene in pathogenesis of non-alcoholic steatohepatitis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189223"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"34105","DOI":"10.1074\/jbc.273.51.34105","article-title":"Hepatocyte nuclear factor-4 controls transcription from a TATA-less human sex hormone-binding globulin gene promoter","volume":"273","author":"Hammond","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1210\/me.2007-0531","article-title":"Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs","volume":"23","author":"Xie","year":"2009","journal-title":"Mol. Endocrinol. Baltim. Md."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1210\/er.2008-0009","article-title":"Causes and metabolic consequences of Fatty liver","volume":"29","author":"Stefan","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/cen.12360","article-title":"Low serum sex hormone-binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients","volume":"80","author":"Hua","year":"2014","journal-title":"Clin. Endocrinol."},{"key":"ref_125","first-page":"1686","article-title":"Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis","volume":"13","author":"Lazo","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1056\/NEJMc0910143","article-title":"Sex hormone-binding globulin and risk of type 2 diabetes","volume":"361","author":"Stefan","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrendo.2015.189","article-title":"Regulation of metabolism by the innate immune system","volume":"12","author":"Lackey","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2337\/db11-0727","article-title":"Potential role of tumor necrosis factor-\u03b1 in downregulating sex hormone-binding globulin","volume":"61","author":"Lecube","year":"2012","journal-title":"Diabetes"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1210\/me.2012-1152","article-title":"IL1\u03b2 down-regulation of sex hormone-binding globulin production by decreasing HNF-4\u03b1 via MEK-1\/2 and JNK MAPK pathways","volume":"26","author":"Hernandez","year":"2012","journal-title":"Mol. Endocrinol. Baltim. Md."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1095\/biolreprod.111.092593","article-title":"Diverse roles for sex hormone-binding globulin in reproduction","volume":"85","author":"Hammond","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1046\/j.1365-2265.2000.01117.x","article-title":"How common are polycystic ovaries and the polycystic ovarian syndrome in women with Cushing\u2019s syndrome?","volume":"53","author":"Kaltsas","year":"2000","journal-title":"Clin. Endocrinol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1046\/j.1365-2265.2003.01790.x","article-title":"Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia","volume":"58","author":"Wallace","year":"2003","journal-title":"Clin. Endocrinol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1515\/HMBCI.2010.008","article-title":"Sex hormone-binding globulin in congenital adrenal hyperplasia","volume":"1","author":"Hampl","year":"2010","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Paizoni, L., Auer, M.K., Schmidt, H., H\u00fcbner, A., Bidlingmaier, M., and Reisch, N. (2020). Effect of androgen excess and glucocorticoid exposure on metabolic risk profiles in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Steroid Biochem. Mol. Biol., 197.","DOI":"10.1016\/j.jsbmb.2019.105540"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12020-013-9896-z","article-title":"Prolactin and sex steroids levels in congenital lifetime isolated GH deficiency","volume":"44","author":"Menezes","year":"2013","journal-title":"Endocrine"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1365-2265.1994.tb01825.x","article-title":"Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal adenomectomy","volume":"41","author":"Oscarsson","year":"1994","journal-title":"Clin. Endocrinol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1677\/JME-09-0025","article-title":"Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha","volume":"43","author":"Selva","year":"2009","journal-title":"J. Mol. Endocrinol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000348837","article-title":"Increased sex hormone-binding globulin levels in children and adolescents with thyrotoxicosis","volume":"79","author":"Nielsen","year":"2013","journal-title":"Horm. Res. Paediatr."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0025-7125(16)31961-7","article-title":"Gonadal steroids and gonadotropins in hyperthyroidism","volume":"59","author":"Chopra","year":"1975","journal-title":"Med. Clin. N. Am."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1365-2265.1992.tb00956.x","article-title":"Serum levels of free and bound testosterone in hyperthyroidism","volume":"36","author":"Ford","year":"1992","journal-title":"Clin. Endocrinol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/j.1939-4640.1992.tb01641.x","article-title":"Testicular function in hyperthyroidism","volume":"13","author":"Hudson","year":"1992","journal-title":"J. Androl."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000181828","article-title":"Reproductive endocrine functions in men with primary hypothyroidism: Effect of thyroxine replacement","volume":"34","author":"Khurana","year":"1990","journal-title":"Horm. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/0026-0495(79)90194-X","article-title":"Evidence for an adrenal origin of plasma estrogens in alcoholic men","volume":"28","author":"Loriaux","year":"1979","journal-title":"Metabolism"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jhep.2015.07.022","article-title":"Inflammatory regulation of steroid sulfatase: A novel mechanism to control estrogen homeostasis and inflammation in chronic liver disease","volume":"64","author":"Jiang","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/MCG.0b013e3180cabc14","article-title":"Elevated sex hormone binding globulin levels may contribute to sexual dysfunction in men with chronic hepatitis C virus infection","volume":"43","author":"Rao","year":"2009","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/jgh.12935","article-title":"Prediction of prevalent but not incident non-alcoholic fatty liver disease by levels of serum testosterone","volume":"30","author":"Seo","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"758","DOI":"10.14309\/ajg.0000000000000138","article-title":"Sex Hormone-Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife","volume":"114","author":"Sarkar","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"dgz244","DOI":"10.1210\/clinem\/dgz244","article-title":"Serum SHBG Is Associated With the Development and Regression of Nonalcoholic Fatty Liver Disease: A Prospective Study","volume":"105","author":"Wang","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0960-0760(99)00070-9","article-title":"Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane","volume":"69","author":"Rosner","year":"1999","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1210\/en.2016-1312","article-title":"Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A","volume":"157","author":"Guidolin","year":"2016","journal-title":"Endocrinology"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Pi, M., Chen, L., Huang, M.Z., Zhu, W., Ringhofer, B., Luo, J., Christenson, L., Li, B., Zhang, J., and Jackson, P.D. (2008). GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003858"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3062319","DOI":"10.1155\/2018\/3062319","article-title":"Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages","volume":"2018","author":"Yamazaki","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Bourebaba, L., K\u0119pska, M., Qasem, B., Zyzak, M., \u0141yczko, J., Klemens, M., Mularczyk, M., and Marycz, K. (2023). Sex hormone-binding globulin improves lipid metabolism and reduces inflammation in subcutaneous adipose tissue of metabolic syndrome-affected horses. Front Mol Biosci., 10.","DOI":"10.3389\/fmolb.2023.1214961"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Saez-Lopez, C., Villena, J.A., Sim\u00f3, R., and Selva, D.M. (2020). Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice. J. Nutr. Biochem., 85.","DOI":"10.1016\/j.jnutbio.2020.108480"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Goto, S., Hosojima, M., Kabasawa, H., and Saito, A. (2023). The endocytosis receptor megalin: From bench to bedside. Int. J. Biochem. Cell Biol., 157.","DOI":"10.1016\/j.biocel.2023.106393"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.cell.2005.06.032","article-title":"Role of endocytosis in cellular uptake of sex steroids","volume":"122","author":"Hammes","year":"2005","journal-title":"Cell"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1158\/2767-9764.CRC-22-0362","article-title":"Regulation of Prostate Androgens by Megalin and 25-hydroxyvitamin D Status: Mechanism for High Prostate Androgens in African American Men","volume":"3","author":"Garcia","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.tem.2021.05.002","article-title":"Sex hormone-binding globulin: Biomarker and hepatokine?","volume":"32","author":"Simons","year":"2021","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1210\/mend.12.1.0050","article-title":"Human sex hormone-binding globulin gene expression in transgenic mice","volume":"12","author":"Deol","year":"1998","journal-title":"Mol. Endocrinol. Baltim. Md."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1210\/en.2015-1677","article-title":"SHBG-C57BL\/ksJ-db\/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development","volume":"156","author":"Selva","year":"2015","journal-title":"Endocrinology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12020-018-1646-9","article-title":"Downregulation of leptin receptor and kisspeptin\/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity","volume":"62","author":"Zhai","year":"2018","journal-title":"Endocrine"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1530\/EC-17-0240","article-title":"Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice","volume":"7","author":"Sofer","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/joim.13547","article-title":"Pediatric obesity\u2014Long-term consequences and effect of weight loss","volume":"292","author":"Marcus","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","author":"Phelps","year":"2024","journal-title":"Lancet"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/apa.17030","article-title":"Studies in children with obesity in two European treatment centres show a high prevalence of impaired glucose metabolism in the Swedish cohort","volume":"113","author":"Ciba","year":"2024","journal-title":"Acta Paediatr."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Iafusco, D., Franceschi, R., Maguolo, A., Guercio Nuzio, S., Crin\u00f2, A., Delvecchio, M., Iughetti, L., Maffeis, C., Calcaterra, V., and Manco, M. (2023). From Metabolic Syndrome to Type 2 Diabetes in Youth. Children, 10.","DOI":"10.3390\/children10030516"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/S2468-1253(21)00183-7","article-title":"Defining paediatric metabolic (dysfunction)-associated fatty liver disease: An international expert consensus statement","volume":"6","author":"Eslam","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e12897","DOI":"10.1111\/ijpo.12897","article-title":"Sedentary time has a stronger impact on metabolic health than moderate to vigorous physical activity in adolescents with obesity: A cross-sectional analysis of the Beta-JUDO study","volume":"17","author":"Julian","year":"2022","journal-title":"Pediatr. Obes."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"189","DOI":"10.5223\/pghn.2020.23.3.189","article-title":"Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome","volume":"23","author":"Wang","year":"2020","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1210\/jc.2014-2674","article-title":"Strong effect of pubertal status on metabolic health in obese children: A longitudinal study","volume":"100","author":"Reinehr","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40348-021-00113-z","article-title":"Relationship between adiponectin, TNF\u03b1, and SHBG in prepubertal children with obesity","volume":"8","author":"Lerin","year":"2021","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jpeds.2011.01.018","article-title":"Sex hormone-binding globulin, oligomenorrhea, polycystic ovary syndrome, and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24 years","volume":"159","author":"Glueck","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11892-016-0751-5","article-title":"Insulin Resistance of Puberty","volume":"16","author":"Kelsey","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1210\/jc.2007-0231","article-title":"Serum sex hormone-binding globulin levels in healthy children and girls with precocious puberty before and during gonadotropin-releasing hormone agonist treatment","volume":"92","author":"Andersson","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1210\/jc.2014-1452","article-title":"Sex steroids in relation to sexual and skeletal maturation in obese male adolescents","volume":"99","author":"Vandewalle","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1097\/MED.0000000000000160","article-title":"Androgens and obesity in male adolescents","volume":"22","author":"Vandewalle","year":"2015","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"e4187","DOI":"10.1210\/clinem\/dgac484","article-title":"A Shifting Relationship Between Sex Hormone-Binding Globulin and Total Testosterone Across Puberty in Boys","volume":"107","author":"Liao","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/ije\/dyv093","article-title":"Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: Observational and causal effect estimates","volume":"44","author":"Wang","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.metabol.2008.10.006","article-title":"Parental history of type 2 diabetes mellitus, metabolic syndrome, and cardiometabolic risk factors in Asian Indian adolescents","volume":"58","author":"Anjana","year":"2009","journal-title":"Metabolism"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.metabol.2009.04.041","article-title":"Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India","volume":"58","author":"Mathias","year":"2009","journal-title":"Metabolism"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ypmed.2005.08.001","article-title":"Body mass index and lipid levels in children from Ankara, Turkey versus Bogalusa, Louisiana","volume":"41","author":"Agirbasli","year":"2005","journal-title":"Prev. Med."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Wee, B.S., Poh, B.K., Bulgiba, A., Ismail, M.N., Ruzita, A.T., and Hills, A.P. (2011). Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study. BMC Public Health, 11.","DOI":"10.1186\/1471-2458-11-333"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1111\/j.1651-2227.2008.00955.x","article-title":"Ethnic differences in metabolic syndrome among overweight and obese children and adolescents: The Oslo Adiposity Intervention Study","volume":"97","author":"Kolsgaard","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1161\/01.CIR.96.12.4319","article-title":"Summary measures of the insulin resistance syndrome are adverse among Mexican-American versus non-Hispanic white children: The Corpus Christi Child Heart Study","volume":"96","author":"Batey","year":"1997","journal-title":"Circulation"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1089\/omi.2013.0066","article-title":"Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort: Lessons learned on LPL, CETP, LIPC, ABCA1, and SHBG","volume":"17","author":"Agirbasli","year":"2013","journal-title":"Omics J. Integr. Biol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/8\/494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:05Z","timestamp":1760033645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/8\/494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":185,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["metabo15080494"],"URL":"https:\/\/doi.org\/10.3390\/metabo15080494","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}