Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

Abstract

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 b-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 b-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.

Regulation of catecholamine synthesizing enzyme gene expression in human pheochromocytoma

“…The data obtained in this study in general resemble the ones by Isobe et al (1). Thus, there was a very high correlation between TH mRNA and total catecholamine content.…”

“…contains an important report investigating the expression of the mRNAs coding for catecholamine synthesizing enzymes in human pheochromocytomas (1). Despite all efforts to characterize these tumors by molecular biological techniques and to study the expression of various growth factors and their receptors, investigations into the genuine enzymes have so far been surprisingly scarce.…”

Catecholamine-Synthesizing Enzymes in Carcinoid Tumors and Pheochromocytomas

“…Immunohistochemistry performed on a specimen of one midgut carcinoid tumor showed positive staining for TH, whereas staining for DBH and PNMT was negative (7 ). Other studies addressing AADC, the enzyme implicated in both the catecholamine and the serotonin metabolic pathways, showed expression in both carcinoids (21)(22)(23) and pheochromocytomas (8,22 ). Our study reveals a similar pattern of diffuse cytoplasmic staining in both carcinoids and pheochromocytomas.…”

“…The rate of catecholamine synthesis is determined by TH (4 ). These enzymes are detectable in pheochromocytomas by immunohistochemical methods (5)(6)(7)(8). Although catecholamines are the principal metabolic product of pheochromocytoma, these tumors also can lead to increased serotonin metabolism (9 ).…”

PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

“…It is well established that 5-HT is synthesized from tryptophan through hydroxylation and decarboxylation, involving the limiting enzyme Tph and the ubiquitous and nonspecific enzyme aromatic L-amino acid decarboxylase, respectively. Aromatic L-amino acid decarboxylase is known to be expressed in the normal adrenal and PPNAD tissues (26,36,37). Interestingly, we found that Tph2, normally present in the brain, was expressed in PPNAD tissues, leading to 5-HT synthesis by a subpopulation of steroidogenic cells.…”