Hospices Civils de Lyon, Fédération d'Endocrinologie, Groupement Hospitalier Est, Bron, France.
Mol Cell Endocrinol. 2010 Mar 5;316(1):53-9. doi: 10.1016/j.mce.2009.09.020. Epub 2009 Sep 26.
Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Plasma SHBG is secreted by the liver under the control of hormones and nutritional factors. In the human hepatoma cell line (HepG2), thyroid and estrogenic hormones, and a variety of drugs including the antioestrogen tamoxifen, the phytoestrogen, genistein and mitotane (Op'DDD) increase SHBG production and SHBG gene promoter activity. In contrast, monosaccharides (glucose or fructose) effectively decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4alpha levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPARgamma antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder-associated diseases early in life.
性激素结合球蛋白（SHBG）是血浆中甾体性激素的主要转运结合蛋白，调节其与靶细胞的亲和力。SHBG 由肝脏在激素和营养因素的控制下分泌。在人肝癌细胞系（HepG2）中，甲状腺和雌激素以及包括抗雌激素他莫昔芬、植物雌激素金雀异黄素和米托坦（Op'DDD）在内的各种药物增加 SHBG 的产生和 SHBG 基因启动子活性。相比之下，单糖（葡萄糖或果糖）通过诱导脂肪生成有效降低 SHBG 的表达，从而降低肝脏 HNF-4alpha 水平，HNF-4alpha 是控制 SHBG 启动子的关键转录因子。有趣的是，减少肝脂肪生成和游离脂肪酸的肝脏生物合成似乎也与甲状腺激素和 PPARgamma 拮抗剂对 SHBG 表达的积极影响有关。该机制为 SHBG 是胰岛素抵抗和代谢综合征的敏感生物标志物，以及为什么低血浆 SHBG 水平是发展为高血糖和 2 型糖尿病的危险因素提供了生物学解释，尤其是在女性中。这些关于肝脏中 SHBG 表达调控的知识的重要进展为早期识别和预防与代谢紊乱相关的疾病提供了新的方法。
