ZONA FASCICULATA-LIKE CELLS DETERMINE THE RESPONSE OF PLASMA-ALDOSTERONE TO METOCLOPRAMIDE AND ALDOSTERONE SYNTHASE MESSENGER-RIBONUCLEIC-ACID LEVEL IN ALDOSTERONE-PRODUCING ADENOMA

The different responses of plasma aldosterone to ACTH and angiotensin II in aldosterone-producing adenoma (APA) is thought to be due to the various cellular compositions of the tumors. To investigate whether the dopaminergic regulation of aldosterone in APA is also dependent on the cellular types, we studied the effects of metoclopramide on plasma aldosterone in six patients with APA. The messenger RNA (mRNA) levels of aldosterone synthase (P450aIdo), 11 beta-hydroxylase (P45011 beta), and 17 alpha-hydroxylase (P45017 alpha) of APA and normal adrenal glands were determined by competitive polymerase chain reaction. After administration of metoclopramide (an antagonist of dopamine-2 receptor), the increment of plasma aldosterone correlated inversely with the percentage of zona fasciculata cells of APA. The mRNA level of P450aldo in the tumorous portion was much higher, whereas the levels of P45011 beta and P45017 alpha mRNAs were lower, than those of the nontumorous portion and normal adrenals. There was a correlation of the percentage of zona fasciculata cells in APA with the levels of P450aldo and P45011 beta mRNAs, but not with P45017 alpha mRNA. These results suggest that differential responsiveness of plasma aldosterone to metoclopramide may be due to various proportions of different cell types in APA that may have different expression of dopamine-2 receptor. In addition, this histologically dependent expression was present at the transcriptional level of the gene responsible for aldosterone biosynthesis.