In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

中文翻译：

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经典和新型性激素结合球蛋白对男性心血管系统的影响

在男性中，70% 的循环睾酮与血浆性激素结合球蛋白 (SHBG) 具有高亲和力，这决定了其在靶细胞中的生物利用度。近年来，越来越多的证据表明，循环 SHBG 不仅是类固醇激素的被动载体，而且还通过假定的质膜受体和雄激素结合蛋白的局部表达来主动调节睾酮信号传导，以达到局部升高的睾酮浓度在特定的雄激素靶组织中。循环 SHBG 水平受代谢和激素因素的影响，肥胖和胰岛素抵抗降低，这表明 SHBG 在评估心血管疾病风险方面可能具有更广泛的临床用途。重要的，血浆 SHBG 水平与睾酮浓度密切相关，在男性中，低睾酮水平与不利的心脏代谢特征相关。尽管肥胖和胰岛素抵抗与心血管疾病的发病率增加有关，但它们是否导致循环 SHBG 的异常表达或其与雄激素信号传导的相互作用仍有待阐明。SHBG 主要在肝脏中产生，但也可以在多种组织中表达，包括脑、脂肪组织和心肌。SHBG 的表达受过氧化物酶体增殖物激活受体控制 它们是否导致循环 SHBG 的异常表达或其与雄激素信号传导的相互作用仍有待阐明。SHBG 主要在肝脏中产生，但也可以在多种组织中表达，包括脑、脂肪组织和心肌。SHBG 的表达受过氧化物酶体增殖物激活受体控制 它们是否导致循环 SHBG 的异常表达或其与雄激素信号传导的相互作用仍有待阐明。SHBG 主要在肝脏中产生，但也可以在多种组织中表达，包括脑、脂肪组织和心肌。SHBG 的表达受过氧化物酶体增殖物激活受体控制γ (PPAR γ ) 和 AMP 活化蛋白激酶 (AMPK)。AMPK/PPAR 相互作用对调节肝细胞核因子 4 (HNF4) 至关重要，这是 SHBG 上调的先决条件。在心肌细胞中，睾酮激活 AMPK 和 PPAR。因此，对心脏 SHBG 的局部表达及其循环水平的描述可能有助于解释雄激素在不同组织中的生理和不利心脏代谢作用。根据新出现的临床证据，在这里，我们将讨论具有心脏保护作用和 SHBG 水平的潜在机制，可用作男性早期代谢和心血管生物标志物。