Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma

Annika M A Berends*, Graeme Eisenhofer, Lauren Fishbein, Anouk N A V D Horst-Schrivers, Ido P Kema, Thera P Links, Jacques W M Lenders, Michiel N Kerstens

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    42 Citations (Scopus)
    407 Downloads (Pure)

    Abstract

    The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression.

    Original languageEnglish
    Article number1121
    Number of pages33
    JournalCancers
    Volume11
    Issue number8
    DOIs
    Publication statusPublished - 6-Aug-2019

    Keywords

    • PPGL
    • catecholamines
    • adrenomedullary function
    • PHENYLETHANOLAMINE-N-METHYLTRANSFERASE
    • VASOACTIVE-INTESTINAL-PEPTIDE
    • AMINO-ACID DECARBOXYLASE
    • HIPPEL-LINDAU-SYNDROME
    • MULTIPLE SIGNALING PATHWAYS
    • DIFFERENT HEREDITARY FORMS
    • NEUROPEPTIDE-Y EXPRESSION
    • CHROMOGRANIN-A FRAGMENT
    • GENE-RELATED PEPTIDE
    • TYROSINE-HYDROXYLASE

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