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.