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).
abstract: BACKGROUND
  The regulation and role of SHBG in children are poorly defined. Here we investigated whether adiposity-related mechanisms regulate SHBG and whether SHBG levels are associated with the age of puberty.
  
  
  METHODS
  Longitudinal modelling of annual physiological and endocrine measurements from age 5 to 15 years in a cohort of 347 Plymouth schoolchildren.
  
  
  RESULTS
  SHBG levels were highest at age 5 years and then declined. Mean (SE) SHBG levels were higher in boys than girls at age 5 years [mean (SE) difference 7.68 (3.80) nmol/L; P = .045] but lower in boys by age 15 years [difference 12.19 (3.4) nmol/L; P < .001]. SHBG correlated inversely with adiposity [body mass index SD score (BMI SDS)], insulin, IGF-I, C-reactive protein (CRP), and leptin and positively with adiponectin but not with dehydroepiandrosterone sulphate, androstenedione, or T. In linear mixed models, five adiposity-related covariates (insulin, leptin, adiponectin, IGF-I, and CRP) all exerted significant main effects on SHBG (boys P = .04 to < .001; girls P = .007 to < .001). However, the further addition of BMI SDS rendered the effects of leptin, insulin, and adiponectin nonsignificant, whereas CRP and IGF-I remained significant. In separate models, the individual effects on SHBG of insulin, leptin, IGF-I, and adiponectin, but not CRP, were displaced by BMI SDS. Finally, in linear regression, BMI SDS little affected R(2) resulting from the five adiposity-related signals. Girls with lower SHBG levels at age 5 years reached Tanner stage 2 earlier, tended to have earlier LH secretion, and earlier age at peak height velocity and menarche. In contrast, boys with lower SHBG levels at age 5 years reached Tanner stage 2 earlier, but there were no relationships between SHBG and earlier onset of LH secretion or age at peak height velocity.
  
  
  CONCLUSIONS
  Adiposity-related endocrine mechanisms and chronic inflammation were associated with the prepubertal decline of SHBG, and lower SHBG levels anticipated earlier puberty. These findings may be relevant to the occurrence of earlier puberty in recent decades.
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Centre for Clinical Trials and Population Studies, Obesity and Metabolism Research Group, University Medicine, Plymouth PL6 8DH, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pinkney
authors.forename: Adam
authors.initials: A
authors.lastname: Streeter
authors.forename: Joanne
authors.initials: J
authors.lastname: Hosking
authors.forename: Mohammod
authors.initials: M
authors.lastname: Mostazir
authors.forename: Mostafir
authors.initials: M
authors.lastname: Mohammod
authors.forename: Alison
authors.initials: A
authors.lastname: Jeffery
authors.forename: Terence
authors.initials: T
authors.lastname: Wilkin
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000293:Adolescent; D000367:Age Factors; D000728:Androgens / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011627:Puberty / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*
chemical_list: D000728:Androgens; D007328:Insulin; D020738:Leptin; D012738:Sex Hormone-Binding Globulin; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D002097:C-Reactive Protein