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Endocrinology. 2018 Mar 1;159(3):1511-1524. doi: 10.1210/en.2018-00064.

High-Resolution Tissue Mass Spectrometry Imaging Reveals a Refined Functional Anatomy of the Human Adult Adrenal Gland.

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Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Department of Internal Medicine, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Institut für Pathologie, University of Würzburg, Würzburg, Germany.
Institut für Pathologie, Universität Bern, Bern, Switzerland.
Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
Clinical Chemistry and Laboratory Medicine, University Hospital Würzburg, Würzburg, Germany.


In the adrenal gland, neuroendocrine cells that synthesize catecholamines and epithelial cells that produce steroid hormones are united beneath a common organ capsule to function as a single stress-responsive organ. The functional anatomy of the steroid hormone-producing adrenal cortex and the catecholamine-producing medulla is ill defined at the level of small molecules. Here, we report a comprehensive high-resolution mass spectrometry imaging (MSI) map of the normal human adrenal gland. A large variety of biomolecules was accessible by matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI, including nucleoside phosphates indicative of oxidative phosphorylation, sterol and steroid metabolites, intermediates of glycolysis and the tricarboxylic acid cycle, lipids, and fatty acids. Statistical clustering analyses yielded a molecularly defined adrenal anatomy of 10 distinct molecular zones including a highly structured corticomedullary interface. By incorporating pathway information, activities of carbohydrate, amino acid, and lipid metabolism as well as endocrine bioactivity were revealed to be highly spatially organized, which could be visualized as different molecularly defined zones. Together, these findings provide a molecular definition of human adult adrenal gland structure beyond classical histological anatomy.

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