ZONA FASCICULATA-LIKE CELLS DETERMINE THE RESPONSE OF PLASMA-ALDOSTERONE TO METOCLOPRAMIDE AND ALDOSTERONE SYNTHASE MESSENGER-RIBONUCLEIC-ACID LEVEL IN ALDOSTERONE-PRODUCING ADENOMA
Kd. Wu et al., ZONA FASCICULATA-LIKE CELLS DETERMINE THE RESPONSE OF PLASMA-ALDOSTERONE TO METOCLOPRAMIDE AND ALDOSTERONE SYNTHASE MESSENGER-RIBONUCLEIC-ACID LEVEL IN ALDOSTERONE-PRODUCING ADENOMA, The Journal of clinical endocrinology and metabolism, 80(3), 1995, pp. 783-789
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 th
e dopaminergic regulation of aldosterone in APA is also dependent on t
he 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 gla
nds were determined by competitive polymerase chain reaction. After ad
ministration of metoclopramide (an antagonist of dopamine-2 receptor),
the increment of plasma aldosterone correlated inversely with the per
centage of zona fasciculata cells of APA. The mRNA level of P450aldo i
n the tumorous portion was much higher, whereas the levels of P45011 b
eta and P45017 alpha mRNAs were lower, than those of the nontumorous p
ortion and normal adrenals. There was a correlation of the percentage
of zona fasciculata cells in APA with the levels of P450aldo and P4501
1 beta mRNAs, but not with P45017 alpha mRNA. These results suggest th
at 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, th
is histologically dependent expression was present at the transcriptio
nal level of the gene responsible for aldosterone biosynthesis.