Department of Medicine, Division of Rheumatology, USA; Department of Dermatology, USA.
Department of Dermatology, USA; Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, USA.
Mol Cell Endocrinol. 2021 Jun 15;530:111238. doi: 10.1016/j.mce.2021.111238. Epub 2021 Mar 12.
CYP11A1, a member of the cytochrome P450 family, plays several key roles in the human body. It catalyzes the first and rate-limiting step in steroidogenesis, converting cholesterol to pregnenolone. Aside from the classical steroidogenic tissues such as the adrenals, gonads and placenta, CYP11A1 has also been found in the brain, gastrointestinal tract, immune systems, and finally the skin. CYP11A1 activity in the skin is regulated predominately by StAR protein and hence cholesterol levels in the mitochondria. However, UVB, UVC, CRH, ACTH, cAMP, and cytokines IL-1, IL-6 and TNFα can also regulate its expression and activity. Indeed, CYP11A1 plays several critical roles in the skin through its initiation of local steroidogenesis and specific metabolism of vitamin D, lumisterol, and 7-dehydrocholesterol. Products of these pathways regulate the protective barrier and skin immune functions in a context-dependent fashion through interactions with a number of receptors. Disturbances in CYP11A1 activity can lead to skin pathology.
CYP11A1 是细胞色素 P450 家族的成员，在人体中发挥着多种关键作用。它催化类固醇生成的第一步和限速步骤，将胆固醇转化为孕烯醇酮。除了经典的类固醇生成组织如肾上腺、性腺和胎盘外，CYP11A1 也存在于大脑、胃肠道、免疫系统，最后是皮肤中。皮肤中的 CYP11A1 活性主要受 StAR 蛋白和线粒体中的胆固醇水平调节。然而，UVB、UVC、CRH、ACTH、cAMP 和细胞因子 IL-1、IL-6 和 TNFα 也可以调节其表达和活性。事实上，CYP11A1 通过启动局部类固醇生成和维生素 D、lumisterol 和 7-脱氢胆固醇的特异性代谢，在皮肤中发挥着几种关键作用。这些途径的产物通过与许多受体相互作用，以依赖于上下文的方式调节保护屏障和皮肤免疫功能。CYP11A1 活性的紊乱可导致皮肤病理学。
