Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?

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Version: author
Serval ID
serval:BIB_26B1C674A53D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?
Journal
Plos One
Author(s)
Grouzmann E., Tschopp O., Triponez F., Matter M., Bilz S., Brändle M., Drechser T., Sigrist S., Zulewski H., Henzen C., Fischli S., Abid K.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
5
Pages
e0125426
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL.
Keywords
Adolescent, Adrenal Gland Neoplasms/genetics, Adrenal Gland Neoplasms/metabolism, Adult, Aged, Catecholamines/metabolism, Child, Dexamethasone/pharmacology, Dopamine beta-Hydroxylase/biosynthesis, Dopamine beta-Hydroxylase/genetics, Epinephrine/biosynthesis, Female, Humans, Male, Metanephrine/metabolism, Middle Aged, Norepinephrine/metabolism, Paraganglioma/genetics, Paraganglioma/metabolism, Phenylethanolamine N-Methyltransferase/biosynthesis, Phenylethanolamine N-Methyltransferase/genetics, Pheochromocytoma/genetics, Pheochromocytoma/metabolism, RNA, Messenger/biosynthesis, Tumor Cells, Cultured, Tyrosine 3-Monooxygenase/biosynthesis, Tyrosine 3-Monooxygenase/genetics, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
05/06/2015 16:23
Last modification date
20/08/2019 13:05
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