In situ Metabolite Mass Spectrometry Imaging: New Insights into the Adrenal Gland

Abstract

The adrenal gland integrates catecholamine-producing neuroendocrine cells and steroid-producing cells with mesenchymal origin in a structured manner under one capsule and is a key regulator for vital bioactivity. In addition to adrenal-specific disease, dysregulation of adrenal hormones is associated with systemic effects, leading to undesirable metabolic and cardiovascular consequences. Mass spectrometry imaging (MSI) technique can simultaneously measure a broad range of biomolecules, including metabolites and hormones, which has enabled the study of tissue metabolic and hormone alterations in adrenal and adrenal-related diseases. Furthermore, this technique coupled with labeled immunohistochemistry staining has enabled the study of the pathophysiological adaptation of the adrenal gland under normal and abnormal conditions at different molecular levels. This review discusses the recent applications of in situ MSI in the adrenal gland. For example, the combination of formalin-fixed paraffin-embedded tissue microarray and MSI to tissues from patient cohorts has facilitated the discovery of clinically relevant prognostic biomolecules and generated promising hypotheses for new sights into physiology and pathophysiology of adrenal gland. MSI also has enabled the discovery of clinically significant tissue molecular (i. e., biomarker) and pathway changes in adrenal disease, particularly in adrenal tumors. In addition, MSI has advanced the ability to optimally identify and detect adrenal gland specific molecules. Thus, as a novel analytical methodology, MSI has provided unprecedented capabilities for in situ tissue study.

Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation

“…In situ matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a novel technique that can simultaneously measure up to thousands of molecules in a single tissue section. The detected molecules encompass metabolites, lipids, glycans, peptides and proteins, as well as drugs and their metabolites ( 96 ). The approach allows co-integration of the detected molecules with conventional hematoxylin and eosin staining or immunohistochemistry and thus enables the spatial visualization of metabolite distribution, and other molecules including hormones, in the context of morphology or protein expression.…”

Steroid Sulfation in Adrenal Tumors

“…To our knowledge, the actual sulfosteroid metabolome of healthy and diseased adrenal glands still needs to be mapped out. Endeavors that use different mass spectrometry (MS) imaging approaches of healthy and cancerous adrenals have recently been reviewed (36). Alongside the abundant DHEAS, pregnenolone sulfate and cholesterol sulfate have been identified as adrenal steroid sulfate species (36).…”

“…Endeavors that use different mass spectrometry (MS) imaging approaches of healthy and cancerous adrenals have recently been reviewed (36). Alongside the abundant DHEAS, pregnenolone sulfate and cholesterol sulfate have been identified as adrenal steroid sulfate species (36). A targeted metabolomics study led by Adina Turcu added pregnenolone sulfate and 5-androstenediol-3-sulfate to the list of products of the healthy adrenal (37).…”

Progress in Primary Aldosteronism 2019: New Players on the Block?

“…In an original publication, Handgriff et al analyze the association between glucocorticoid co-secretion, assessed by the 1 mg dexamethasone suppression test, on the prevalence and the time course of thyroid antibodies in PA [13]. In a series of pathophysiologic manuscripts, the role of mast cells [14], expression of aldosterone synthase in adrenalectomy samples [15], the role of aldosterone producing cell clusters [16], and the methodologic advances obtained by tissue mass spectrometry imaging [17] are analyzed. Finally, the study of Gao et al [18] gives a comprehensive overview on calcium metabolism in PA, followed by an in-depth study on clinical determinants of surgical success by Naruse et al [19].…”