Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.
OBJECTIVE
Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) produce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines - the noradrenaline transporter and the vesicular monoamine transporters (VMAT 1 and VMAT 2).


METHODS
Tumour tissue and plasma samples were obtained from 31 patients with hereditary phaeochromocytoma - 18 with VHL syndrome and 13 with MEN 2. We used quantitative PCR, Western blotting, electron microscopy, immunohistochemistry and measurements of plasma and tumour catecholamines to assess differences in expression of the transporters in noradrenaline-producing vs adrenaline-producing hereditary tumours. These differences were compared with those in a further group of 26 patients with non-syndromic phaeochromocytoma.


RESULTS
Adrenaline-producing phaeochromocytomas in MEN 2 patients expressed more noradrenaline transporter mRNA and protein than noradrenaline-producing tumours in VHL patients. In contrast, there was greater expression of VMAT 1 in VHL than MEN 2 tumours, while expression of VMAT 2 did not differ significantly. These differences were associated with larger numbers of storage vesicles and higher tissue contents of catecholamines in MEN 2 than in VHL tumours. Differences in expression of the noradrenaline transporter were weaker, and those of VMAT 1 and VMAT 2 stronger, in noradrenaline and adrenaline-producing non-syndromic than in hereditary tumours.


CONCLUSIONS
The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.
Huynh
Thanh-Truc
TT
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pacak
Karel
K
Brouwers
Frederieke M
FM
Abu-Asab
Mones S
MS
Worrell
Robert A
RA
Walther
Macclellan M
MM
Elkahloun
Abdel G
AG
Goldstein
David S
DS
Cleary
Susannah
S
Eisenhofer
Graeme
G
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010673:Pheochromocytoma / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D050492:Vesicular Biogenic Amine Transport Proteins / Q000378:metabolism; D006623:von Hippel-Lindau Disease / Q000150:complications*
D050482:Catecholamine Plasma Membrane Transport Proteins; D002395:Catecholamines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins