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Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas
1Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
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.
Insights
Catecholamine synthesis in pheochromocytomas is controlled by gene expression levels. Tyrosine hydroxylase mRNA levels correlate with catecholamine content in these tumors.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Pheochromocytomas are tumors that synthesize and release catecholamines.
- Catecholamine release is linked to various clinical manifestations.
Purpose of the Study:
- To elucidate the molecular mechanisms controlling catecholamine synthesis in pheochromocytomas.
Main Methods:
- Measured mRNA concentrations of catecholamine-synthesizing enzymes (tyrosine hydroxylase, AADC, DBH, PNMT) and catecholamine content.
- Compared 12 pheochromocytomas with 12 normal adrenal medullas.
Main Results:
- Pheochromocytomas showed increased tyrosine hydroxylase, AADC, and DBH mRNA but decreased PNMT mRNA compared to normal adrenal medullas.
- Tyrosine hydroxylase mRNA expression correlated significantly with total catecholamine content in pheochromocytomas (r=0.964, P<0.0001).
Conclusions:
- Catecholamine production in pheochromocytomas is primarily regulated at the gene expression level.