title: Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?
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.
authors.affiliation: Service of Biomedicine, Catecholamine and Peptides Laboratory, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tschopp
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospital Geneva (HUG), Geneva, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triponez
authors.affiliation: Division of Visceral Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Matter
authors.affiliation: Clinic for Endocrinology, Diabetes, Bone disease and Metabolism, KantonsSpital St. Gallen, St. Gallen, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bilz
authors.affiliation: Clinic for Endocrinology, Diabetes, Bone disease and Metabolism, KantonsSpital St. Gallen, St. Gallen, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Brändle
authors.affiliation: Clinic for Endocrinology, Diabetes, Bone disease and Metabolism, KantonsSpital St. Gallen, St. Gallen, Switzerland.
authors.forename: Tilman
authors.initials: T
authors.lastname: Drechser
authors.affiliation: Clinic for Endocrinology, Diabetes, Bone disease and Metabolism, KantonsSpital St. Gallen, St. Gallen, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sigrist
authors.affiliation: Division for Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Zulewski
authors.affiliation: Division of Endocrinology and Diabetes, KantonsSpital Luzern, Luzern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.affiliation: Division of Endocrinology and Diabetes, KantonsSpital Luzern, Luzern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischli
authors.affiliation: Service of Biomedicine, Catecholamine and Peptides Laboratory, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Karim
authors.initials: K
authors.lastname: Abid
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000378:metabolism*; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D004837:Epinephrine / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D002395:Catecholamines; D012333:RNA, Messenger; D008676:Metanephrine; D003907:Dexamethasone; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D009638:Norepinephrine; D004837:Epinephrine