Department of Psychology, University of Toronto, Toronto, Ontario, M5S 3G3, Canada.
Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal, Quebec, H3T 1C5, Canada.
J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4187-e4196. doi: 10.1210/clinem/dgac484.
Sex hormone-binding globulin (SHBG) is associated with levels of total testosterone (total-T), and both total-T and SHBG are associated with obesity.
We aimed to clarify the nature of the relationship between testosterone and SHBG and improve our understanding of their relationships with obesity. We hypothesize that the hypothalamic-pituitary-gonadal axis contributes to the homeostasis of testosterone by increasing the production of gonadal testosterone through a feedback mechanism that might operate differently at different pubertal stages.
We investigated the dynamics of the relationship between SHBG, total-T, and body mass index (BMI) throughout puberty (from age 9 to 17) using longitudinal data obtained in 507 males. The directionality of this relationship was explored using polygenic scores of SHBG and total-T, and a two-sample Mendelian Randomization (MR) in male adults.
Consistent with our hypothesis, we found positive relationships between SHBG and total-T at age 15 and 17 but either no relationship or a negative relationship during the earlier time points. Such shifting relationships explained age-related changes in the association between total-T and BMI. Polygenic scores of SHBG and total-T in mediation analyses and the two-sample MR in male adults suggested an effect of SHBG on total-T but also a somewhat weaker effect of total-T on SHBG. Two-sample MR also showed an effect of BMI on SHBG but no effect of SHBG on BMI.
These results clarify the nature of the relationship between testosterone and SHBG during puberty and adulthood and shed new light on their possible relationship with obesity.
性激素结合球蛋白（SHBG）与总睾酮（total-T）水平相关，而总-T 和 SHBG 均与肥胖相关。
我们旨在阐明睾酮和 SHBG 之间关系的本质，并加深对它们与肥胖关系的理解。我们假设，通过反馈机制，下丘脑-垂体-性腺轴可能在不同的青春期阶段以不同的方式发挥作用，从而促进性腺睾酮的产生，以此来维持睾酮的体内平衡。
我们使用 507 名男性的纵向数据，研究了 SHBG、总-T 和体重指数（BMI）在整个青春期（9 岁至 17 岁）过程中的动态关系。我们使用 SHBG 和总-T 的多基因评分，以及男性成年人的两样本 Mendelian Randomization（MR），探索了这种关系的方向性。
与我们的假设一致，我们发现 SHBG 和总-T 在 15 岁和 17 岁时呈正相关，但在更早的时间点则没有关系或呈负相关。这种变化的关系解释了总-T 与 BMI 之间相关性的年龄变化。中介分析中的 SHBG 和总-T 的多基因评分，以及男性成年人的两样本 MR 表明，SHBG 对总-T 有影响，而总-T 对 SHBG 的影响则稍弱。两样本 MR 还显示 BMI 对 SHBG 有影响，但 SHBG 对 BMI 没有影响。
这些结果阐明了青春期和成年期睾酮和 SHBG 之间关系的本质，并为它们与肥胖的可能关系提供了新的认识。
