Pheochromocytomas synthesize and release catecholamines, which subsequently are 
related to various clinical manifestations of the disease. However, 
pheochromocytomas are not innervated and the catecholamine release and synthesis 
are not initiated by neural impulses. It is still unknown how catecholamine 
synthesis is regulated in pheochromocytomas. As a first step toward 
understanding the molecular mechanisms by which catecholamine synthesis is 
controlled in the tumor, we measured the levels of mRNA coding for the 
catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines 
in 6 pheochromocytomas and 2 normal adrenal glands. The TH mRNA level was 
overexpressed and the catecholamine contents were high in 4 out of 6 
pheochromocytomas. There was a close correlation between the TH mRNA level and 
the catecholamines content in the tumors. We also examined the gene expression 
of the messengers of other catecholamine synthesizing enzymes, dopamine 
beta-hydroxylase (DBH) and aromatic 1-amino acid decarboxylase (AADC) in 
pheochromocytomas. The expression of these genes was in parallel with that of TH 
mRNA in the tumors. These findings indicate that catecholamine overproduction in 
pheochromocytomas is mediated by the overexpression of genes coding for 
catecholamines synthesizing enzymes, TH, DBH, and AADC.