School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea; Department of Bionano Engineering and Bionanotechnology, Hanyang University, Ansan, 15588, Republic of Korea.
Department of Physics and Astronomy, Seoul National University, Seoul, 08826, Republic of Korea.
Biosens Bioelectron. 2020 Apr 15;154:112071. doi: 10.1016/j.bios.2020.112071. Epub 2020 Feb 3.
In the neuroendocrine system, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) play important roles in the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Disorders of the HPA system lead to physiological problems, such as Addison's disease and Cushing's syndrome. Therefore, detection of CRH and ACTH is essential for diagnosing disorders related to the HPA system. Herein, receptors of the HPA axis were used to construct a bioelectronic sensor system for the detection of CRH and ACTH. The CRH receptor, corticotropin-releasing hormone receptor 1 (CRHR1), and the ACTH receptor, melanocortin 2 receptor (MC2R), were produced using an Escherichia coli expression system, and were reconstituted using nanodisc (ND) technology. The receptor-embedded NDs were immobilized on a floating electrode of a carbon nanotube field-effect transistor (CNT-FET). The constructed sensors sensitively detected CRH and ACTH to a concentration of 1 fM with high selectivity in real time. Furthermore, the reliable detection of CRH and ACTH in human plasma by the developed sensors demonstrated their potential in clinical and practical applications. These results indicate that CRHR1 and MC2R-based bioelectronic sensors can be applied for rapid and efficient detection of CRH and ACTH.
在神经内分泌系统中，促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素（ACTH）在调节下丘脑-垂体-肾上腺（HPA）系统中发挥着重要作用。HPA 系统的紊乱会导致生理问题，如艾迪生病和库欣综合征。因此，检测 CRH 和 ACTH 对于诊断与 HPA 系统相关的疾病至关重要。在此，我们使用 HPA 轴受体构建了一种用于检测 CRH 和 ACTH 的生物电子传感器系统。CRH 受体，即促肾上腺皮质激素释放激素受体 1（CRHR1），和 ACTH 受体，即黑素皮质素 2 受体（MC2R），是使用大肠杆菌表达系统产生的，并通过纳米盘（ND）技术进行了重组。受体嵌入的 ND 被固定在碳纳米管场效应晶体管（CNT-FET）的浮动电极上。所构建的传感器能够实时灵敏地检测到 1 fM 浓度的 CRH 和 ACTH，具有很高的选择性。此外，开发的传感器能够可靠地检测人血浆中的 CRH 和 ACTH，表明其在临床和实际应用中的潜力。这些结果表明，基于 CRHR1 和 MC2R 的生物电子传感器可用于快速、高效地检测 CRH 和 ACTH。
