Primary Cultures and Cell Lines for <i>In Vitro</i> Modeling of the Human Adrenal Cortex

Invited Review for 100^th Anniversary of the TJEM

Primary Cultures and Cell Lines for In Vitro Modeling of the Human Adrenal Cortex

Kazutaka Nanba,^1,2 Amy R. Blinder¹ and William E. Rainey^1,3

¹Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
²Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
³Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

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.

Keywords —— adrenal; cell lines; primary monolayer culture; steroidogenesis

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Tohoku J. Exp. Med 2021, 253, 217-232.

Correspondence: William E. Rainey Ph.D., 1150 West Medical Center Dr. Ann Arbor, MI 48109, USA.

e-mail: wer@med.umich.edu