Pinkney Jonathan, Streeter Adam, Hosking Joanne, Mostazir Mohammod, Jeffery Alison, Wilkin Terence
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.
J Clin Endocrinol Metab. 2014 Sep;99(9):3224-32. doi: 10.1210/jc.2013-3902. Epub 2014 Jun 13.
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.
Longitudinal modelling of annual physiological and endocrine measurements from age 5 to 15 years in a cohort of 347 Plymouth schoolchildren.
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.
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.
性激素结合球蛋白（SHBG）在儿童中的调节机制和作用尚不明确。在此，我们研究了与肥胖相关的机制是否调节SHBG，以及SHBG水平是否与青春期年龄相关。
对347名普利茅斯学童从5岁到15岁的年度生理和内分泌测量数据进行纵向建模。
SHBG水平在5岁时最高，然后下降。5岁时男孩的平均（标准误）SHBG水平高于女孩[平均（标准误）差异为7.68（3.80）nmol/L；P = 0.045]，但到15岁时男孩的SHBG水平低于女孩[差异为12.19（3.4）nmol/L；P < 0.001]。SHBG与肥胖[体重指数标准差评分（BMI SDS）]、胰岛素、胰岛素样生长因子-I（IGF-I）、C反应蛋白（CRP）和瘦素呈负相关，与脂联素呈正相关，但与硫酸脱氢表雄酮、雄烯二酮或睾酮无关。在线性混合模型中，五个与肥胖相关的协变量（胰岛素、瘦素、脂联素、IGF-I和CRP）均对SHBG产生显著的主效应（男孩P = 0.04至< 0.001；女孩P = 0.007至< 0.001）。然而，进一步加入BMI SDS后，瘦素、胰岛素和脂联素的效应变得不显著，而CRP和IGF-I仍然显著。在单独的模型中，胰岛素、瘦素、IGF-I和脂联素（而非CRP）对SHBG的个体效应被BMI SDS取代。最后，在线性回归中，BMI SDS对由五个与肥胖相关的信号所导致的R²影响不大。5岁时SHBG水平较低的女孩更早进入坦纳2期，促黄体生成素（LH）分泌往往更早，身高增长峰值速度和月经初潮年龄也更早。相比之下，5岁时SHBG水平较低男性更早进入坦纳2期，但SHBG与LH分泌提前开始或身高增长峰值速度年龄之间没有关联。
与肥胖相关的内分泌机制和慢性炎症与青春期前SHBG水平下降有关，较低的SHBG水平预示着青春期提前。这些发现可能与近几十年来青春期提前的发生有关。
