EXPRESSION OF MESSENGER-RNA CODING FOR 4 CATECHOLAMINE-SYNTHESIZING ENZYMES IN HUMAN ADRENAL PHEOCHROMOCYTOMAS

Objective: To understand the molecular mechanisms by which catecholami ne synthesis is controlled in pheochromocytomas - tumors that synthesi ze and release catecholamines, which are related to various clinical m anifestations of the condition. Methods: We measured the concentration s of mRNA coding for the catechol amine-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 norm al adrenal medullas. Results: The mean content of total catecholamine and the beta-actin mRNA expression in the pheochromocytomas were almos t the same as those in the normal adrenal medullas. However, the tyros ine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocyt omas were greater than those of the normal adrenal medullas. Conversel y. the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsibl e for the difference in the proportions of catecholamines between pheo chromocytomas and normal adrenal medullas, The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude am ong the pheochromocytomas, and the tyrosine hydroxylase mRNA expressio ns correlated with the contents of total catecholamine in the tumors ( r=0.964, P<0.0001). Conclusions: These findings indicate that catechol amine production in pheochromocytomas is primarily controlled by the l evel of gene expression.