Regulation of catecholamine synthesizing enzyme gene expression in human pheochromocytoma

Lehnert, Hendrik

doi:10.1530/eje.0.1380363

Cited by 18 publications

(28 citation statements)

References 12 publications

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“…Ascorbic acid is critical in the biochemical cascade of catecholamine production (Lehnert 1998). In the present series, ascorbic acid was identified as a significant discriminator of PCCs than of the normal medulla and ACCs.…”

Section: Discussionsupporting

confidence: 48%

“…As is well known, the synthesis of adrenaline depends on the presence of phenylethanolamine-N-methyltransferase (PNMT). The levels of PNMT mRNA have been found to be lower in PCC samples than in the normal medulla (Lehnert 1998). This disparity is probably responsible for the difference in catecholamine content between tumors and normal adrenal medulla, leading to higher noradrenaline secretion in PCC samples examined in the present study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

Impériale¹,

Elbayed²,

Moussallieh³

et al. 2013

Endocrine-Related Cancer

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In this study, we i) assessed the metabolic profile of the normal adrenal cortex and medulla of adult human subjects by means of 1 H-high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy; ii) compared the biochemical profile of adenoma (Ad), adrenal cortical carcinoma (ACC), and pheochromocytoma (PCC) samples with that of healthy adrenal tissue samples; and iii) investigated the metabolic differences between ACCs and Ads as well as between ACCs and PCCs. Sixty-six tissue samples (13 adrenal cortical tissue, eight medullary tissue, 13 Ad, 12 ACC, and 20 PCC samples) were analyzed. Adrenaline and noradrenaline were undetectable in cortical samples representing the metabolic signature of the tissue derived from neural crest. Similarity between the metabolic profile of Ads and that of the normal adrenal cortex was shown. Inversely, ACC samples clearly made up a detached group exhibiting the typical stigmata of neoplastic tissue such as choline-containing compounds, biochemical markers of anaerobic processes, and increased glycolysis. Significantly higher levels of lactate, acetate, and total choline-containing compounds played a major role in the differentiation of ACCs from Ads. Moreover, the high fatty acid content of ACCs contributed to the cluster identification of ACCs. Of the 14 sporadic PCC samples, 12 exhibited predominant or exclusive noradrenaline secretion. The noradrenaline: adrenaline ratio was inverted in the normal medullary tissue samples. Multiple endocrine neoplasia type 2-and NF1-related PCC samples exhibited both adrenaline and noradrenaline secretion. In the von Hippel-Lindau disease-related PCC samples, only noradrenaline secretion was detected by HRMAS NMR spectroscopy. This study is one of the first applications of metabolomics to adrenal pathophysiology and it is the largest study to report HRMAS NMR data related to the adrenal cortex and adrenal cortical tumors.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

Impériale¹,

Elbayed²,

Moussallieh³

et al. 2013

Endocrine-Related Cancer

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“…The cell cycle regulating gene p53 exhibits frequent mutations or intronic sequence alterations in malignant, but not in benign, pheocromocytoma (Yoshimoto et al 1998). Loss of heterozygosity has been demonstrated in various regions (1p, 3p, 17p, 22q), which may in¯uence tumor suppressor genes (Lehnert et al 1998).…”

Section: Pathogenesismentioning

confidence: 99%

Clinical management of malignant adrenal tumors

Kopf

Goretzki

Lehnert

2001

Journal of Cancer Research and Clinical Oncology

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Malignant primary adrenal tumors are rare forms of cancer with an estimated incidence of two to ten new cases per one million inhabitants per year. The 5-year survival rate for adrenocortical carcinoma is approximately 35%, whereas the 10-year survival rate of malignant pheochromocytoma reaches 40%. Clinical studies support repeated surgery as the mainstay of treatment, either with curative or palliative intention. For adrenocortical carcinoma, adjunctive treatment with oral mitotane leads to well-documented improvement of survival. Rare malignant pheochromocytomas with distant metastases are preferably treated by 131I-MIBG. Chemotherapy is reserved for unresectable tumors without sufficient response to mitotane or 131I-MIBG, respectively. Cisplatin and etoposide as single therapy, or in combination with doxorubicin or etoposide, appear to be effective in adrenocortical carcinoma. Malignant pheochromocytoma may be treated with vincristine, dacarbazine, and cyclophosphamide. Treatment with octreotide is currently being evaluated. Radiotherapy is indicated if unresectable tumor masses cause local symptoms. If symptoms of endocrine activity are not sufficiently controlled by measures aiming at tumor mass reduction, specific inhibitors of hormone synthesis or action are available. Ketoconazole is widely used for adrenocortical carcinoma, and phenoxybenzamine and metyrosine are available for malignant pheochromocytoma. This review provides guidelines for rational disease management based on still scanty clinical evidence.

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“…The majority of pheochromocytomas are sporadic cases (3 ), but a familial predisposition has been found in, e.g., patients with the multiple endocrine neoplasia (MEN) syndrome type IIa/b (3 ). Catecholamine synthesis depends on three specific enzymes ( Fig.…”

mentioning

confidence: 99%

Catecholamine-Synthesizing Enzymes in Carcinoid Tumors and Pheochromocytomas

Meijer¹,

Copray²,

Hollema

et al. 2003

Clinical Chemistry

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Background: Serotonin is the principal endocrine product of carcinoid tumors, but simultaneously increased production of catecholamines has been described in these tumors. As it is not clear whether these tumors contain specific enzymes for catecholamine synthesis, we aimed to detect catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-␤-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT)] in midgut carcinoid tumors and pheochromocytoma and to correlate enzyme expression to serotonin production as well as catecholamines and metabolites excreted in urine. Methods: Paraffin-embedded tumor specimens from 21 midgut carcinoid patients and 20 pheochromocytoma patients (10 sporadic and 10 MEN type IIa-related tumors) were stained for TH, DBH, and PNMT, using a three-step biotin-avidin-peroxidase method. Results: TH was demonstrated in 9 (43%) of 21 carcinoids and in all (100%) of 20 pheochromocytomas, DBH in 8 (38%) carcinoids and in 15 (75%) pheochromocytomas, and PNMT in 7 (33%) carcinoids and in 13 (65%) pheochromocytomas. Increased urinary excretion of catecholamines and metabolites was observed in 10 (48%) carcinoid patients and in all pheochromocytoma patients. No clinically relevant association between enzyme expression and urinary excretion of catecholamines and metabolites was found. Conclusions: Catecholamine-synthesizing enzymes are present in many carcinoid tumors. This finding possibly indicates the existence of a catecholamine-synthesizing

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Regulation of catecholamine synthesizing enzyme gene expression in human pheochromocytoma

Cited by 18 publications

References 12 publications

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

Clinical management of malignant adrenal tumors

Catecholamine-Synthesizing Enzymes in Carcinoid Tumors and Pheochromocytomas

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