Roozbeh Jamshid, Janfeshan Sahar, Afshari Afsoon, Doostkam Aida, Yaghobi Ramin
Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Int J Mol Cell Med. 2022;11(2):168-179. doi: 10.22088/IJMCM.BUMS.11.2.168. Epub 2022 Dec 12.
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infecting mechanism depends on hosting angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as essential components and androgens as regulators for inducing the expression of these components. Therefore, hyperandrogenism-related disease such as polycystic ovary syndrome (PCOS) in insulin resistant women in reproductive-age is a high-risk factor for SARS-CoV-2 infection. Here, we describe the signaling pathways that might increase the susceptibility and severity of this new pandemic in PCOS women with insulin resistance (IR). Luteinizing hormone and insulin increase the risk of SARS-CoV-2 infection in these patients via the induction of steroidogenic enzymes expression through cAMP-response element binding protein and Forkhead box protein O1 (FOXO1), respectively. TMPRSS2 expression is activated through phosphorylation of FOXO1 in ovaries. In other words, SARS-CoV-2 infection is associated with temporary IR by affecting ACE2 and disturbing β-pancreatic function. Therefore, PCOS, IR, and SARS-CoV-2 infection are three corners of the triangle that have complicated relations, and their association might increase the risk of SARS-CoV-2 infection and severity.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的感染机制依赖于宿主血管紧张素转换酶2（ACE2）和跨膜丝氨酸蛋白酶2（TMPRSS2）作为必需成分，以及雄激素作为诱导这些成分表达的调节剂。因此，育龄期胰岛素抵抗女性中的多囊卵巢综合征（PCOS）等高雄激素血症相关疾病是SARS-CoV-2感染的高危因素。在此，我们描述了可能增加胰岛素抵抗（IR）的PCOS女性对这种新大流行病易感性和严重程度的信号通路。促黄体生成素和胰岛素分别通过环磷酸腺苷反应元件结合蛋白和叉头框蛋白O1（FOXO1）诱导类固醇生成酶表达，从而增加这些患者感染SARS-CoV-2的风险。TMPRSS2的表达通过卵巢中FOXO1的磷酸化而被激活。换句话说，SARS-CoV-2感染通过影响ACE2和干扰β-胰腺功能与暂时性IR相关。因此，PCOS、IR和SARS-CoV-2感染是关系复杂的三角形的三个角，它们之间的关联可能会增加SARS-CoV-2感染的风险和严重程度。
