Department of Molecular and Integrative Physiology, University of Michigan.
Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center.
Tohoku J Exp Med. 2021 Apr;253(4):217-232. doi: 10.1620/tjem.253.217.
The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.
人类肾上腺皮质是一个复杂的内分泌器官，可产生盐皮质激素、糖皮质激素和雄激素。这些类固醇在肾上腺皮质的球状带、束状带和网状带的不同细胞类型中产生。肾上腺类固醇生成异常会导致多种疾病，可导致高血压、代谢综合征、不孕和早熟性肾上腺功能亢进。肾上腺皮质还可发生类固醇生成腺瘤，很少发生肾上腺皮质癌。体外细胞培养模型为研究控制肾上腺皮质生理和病理状况的分子和细胞机制提供了重要工具。此外，肾上腺细胞内存在多种类固醇代谢酶，使其成为定义可能阻断这些酶的内分泌干扰物的模型。可以使用新鲜分离的细胞研究人类肾上腺类固醇产生和细胞分裂/肿瘤生长的调节和失调，但这需要获得大多数研究人员无法获得的人类肾上腺。已证明永生化的人肾上腺皮质细胞系在研究控制肾上腺类固醇生成和肿瘤发生的分子和生化机制方面具有重要价值。目前的人肾上腺细胞系包括原始的 NCI-H295 及其亚系：H295A、H295R、HAC13、HAC15、HAC50 和 H295RA 以及最近建立的 MUC-1、CU-ACC1 和 CU-ACC2。本综述将讨论使用胎儿和成人肾上腺细胞的原代培养以及肾上腺皮质细胞系作为研究人类肾上腺生理学和病理生理学的体外模型的用途。
