Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas.
OBJECTIVE
To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas--tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition.


METHODS
We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas.


RESULTS
The mean content of total catecholamine and the beta-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001).


CONCLUSIONS
These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.
Isobe
K
K
Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Nakai
T
T
Yukimasa
N
N
Nanmoku
T
T
Takekoshi
K
K
Nomura
F
F
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics; D016022:Case-Control Studies; D002395:Catecholamines / Q000096:biosynthesis*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005815:Genetic Code; D006801:Humans; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D002395:Catecholamines; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D001142:Aromatic-L-Amino-Acid Decarboxylases