title: Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma.
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.
authors.affiliation: Division of Health Science, Murdoch University, Perth, Western Australia, 6150, Australia.
authors.forename: Susannah
authors.initials: S
authors.lastname: Cleary
authors.forename: Frederieke M
authors.initials: FM
authors.lastname: Brouwers
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: David L
authors.initials: DL
authors.lastname: Christie
authors.forename: Janusz
authors.initials: J
authors.lastname: Lipski
authors.forename: Alan R
authors.initials: AR
authors.lastname: McNeil
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Phillips
mesh_terms: D000313:Adrenal Medulla / Q000201:enzymology / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis; D019439:Chromaffin Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D010625:Phenylethanolamine N-Methyltransferase / Q000096:biosynthesis* / Q000378:metabolism; D010673:Pheochromocytoma / Q000201:enzymology / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010625:Phenylethanolamine N-Methyltransferase