Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Biochem Biophys Res Commun. 2020 Nov 19;532(4):613-619. doi: 10.1016/j.bbrc.2020.08.100. Epub 2020 Sep 6.
The sex hormone-binding globulin (SHBG) is involved in the onset and progression of insulin resistance and metabolic syndromes, with its expression downregulated in the placental tissues of patients with gestational diabetes mellitus (GDM). However, the underlying mechanisms for these effects remain unclear. In this study, we enrolled an equal number (30) of GDM and non-GDM puerperae who underwent cesarean section at Shengjing Hospital. After due approval by the ethics committee, the expression levels of SHBG and extracellular-signal-regulated kinase (ERK) pathway markers in the placental tissues of these individuals were measured via reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. The correlation analysis of these genes revealed that the expression of SHBG in placental tissues was downregulated and negatively correlated with the expression of ERK pathway markers, which were upregulated in placental tissues. Further investigations using the HTR-8/SVneo trophoblast cell line revealed that the trophoblasts with small interfering RNA (siRNA)-silenced SHBG expression displayed increased mRNA and protein expression levels of ERK pathway markers, as well as reduced apoptosis and enhanced proliferation. In contrast, trophoblasts with high SHBG expression showed a downregulated expression of ERK pathway markers, increased apoptosis, reduced proliferation, and a shorter S phase. Therefore, we believe that SHBG may participate in the onset of insulin resistance and GDM by regulating the activity of the ERK pathway.
性激素结合球蛋白 (SHBG) 参与胰岛素抵抗和代谢综合征的发生和进展，其在妊娠期糖尿病 (GDM) 患者的胎盘组织中表达下调。然而，这些影响的潜在机制尚不清楚。在这项研究中，我们招募了数量相等（30 名）的在盛京医院行剖宫产术的 GDM 和非 GDM 产妇。在伦理委员会的适当批准后，通过逆转录聚合酶链反应 (RT-PCR) 和 Western blot 检测这些个体胎盘组织中 SHBG 和细胞外信号调节激酶 (ERK) 途径标志物的表达水平。这些基因的相关性分析表明，胎盘组织中 SHBG 的表达下调，与胎盘组织中上调的 ERK 途径标志物的表达呈负相关。进一步使用 HTR-8/SVneo 滋养层细胞系进行的研究表明，沉默 SHBG 表达的 siRNA 滋养层细胞系中 ERK 途径标志物的 mRNA 和蛋白表达水平增加，凋亡减少，增殖增强。相比之下，高 SHBG 表达的滋养层细胞系中 ERK 途径标志物的表达下调，凋亡增加，增殖减少，S 期缩短。因此，我们认为 SHBG 可能通过调节 ERK 通路的活性参与胰岛素抵抗和 GDM 的发生。
