Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma |
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Authors: | Susannah Cleary Frederieke M Brouwers Graeme Eisenhofer Karel Pacak David L Christie Janusz Lipski Alan R McNeil Jacqueline K Phillips |
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Institution: | (1) Division of Health Science, Murdoch University, Perth, Western Australia, 6150, Australia;(2) West Australian Biomedical Research Institute, Perth, Western Australia, 6845, Australia;(3) National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1620, USA;(4) National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA;(5) School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand;(6) Division of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand;(7) Dorevitch Pathology, Heidelberg, Victoria, 3084, Australia |
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Abstract: | Expression of the noradrenaline transporter (NAT) was examined in normal human adrenal medulla and phaeochromocytoma by using
immunohistochemistry and confocal microscopy. The enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase
(PNMT) were used as catecholamine biosynthetic markers and chromogranin A (CGA) as a marker for secretory granules. Catecholamine
content was measured by using high performance liquid chromatography (HPLC). In normal human adrenal medulla (n=5), all chromaffin cells demonstrated strong TH, PNMT and NAT immunoreactivity. NAT was co-localized with PNMT and was located
within the cytoplasm with a punctate appearance. Human phaeochromocytomas demonstrated strong TH expression (n=20 samples tested) but variable NAT and PNMT expression (n=24). NAT immunoreactivity ranged from absent (n=3) to weak (n=10) and strong (n=11) and, in some cases, occupied an apparent nuclear location. Unlike the expression seen in normal human adrenal medullary
tissue, NAT expression was not consistently co-localized with PNMT. PNMT also showed highly variable expression that was poorly
correlated with tumour adrenaline content. Immunoreactivity for CGA was colocalized with NAT within the cytoplasm of normal
human chromaffin cells (n=4). This co-localization was not consistent in phaeochromocytoma tumour cells (n=7). The altered pattern of expression for both NAT and PNMT in phaeochromocytoma indicates a significant disruption in the
regulation and possibly in the function of these proteins in adrenal medullary tumours. |
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Keywords: | Immunohistochemistry Tyrosine hydroxylase Catecholamine Chromaffin cells Adrenal medulla Norepinephrine transporter Chromogranin A Human |
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