Although stimulation of aldosterone secretion is one of the functions of angiotensin
II, the gene expression and biological significance of the angiotensin II receptor
subtypes, AT1 and AT2, in the human adrenal have not been characterized. We therefore
investigated the transcription levels of the receptor subtype genes and their roles
in regulation of steroid secretion by human adrenals. The expression of AT1 and AT2
receptor mRNA was assessed by reverse transcription-polymerase chain reaction followed
by Southern blot analysis in normal adrenocortical tissues (n = 6) and a series of
adrenal tumour tissues: aldosterone-producing adrenocortical adenoma (n = 6), Cushing's
syndrome (n = 6) and pheochromocytoma (n = 6). The role of the two receptor subtypes
in steroid secretion in vitro was examined by incubating the tissue with angiotensin II (1 µM) with or without
the selective AT1 antagonist CV-11974 (1 µM). Both AT1 and AT2 receptor mRNA transcripts
were demonstrated in all of the human adrenal tissues tested. Angiotensin II-induced
aldosterone secretion was suppressed 50% upon the addition of CV-11974. The selective
AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control, which
was not suppressed by CV-11974. Angiotensin II and CGP-42112 did not affect cortisol
secretion. These results suggest that both AT2 and AT1 receptors may be involved in
the regulation of aldosterone secretion and tumorigenesis of the human adrenals.
Key words
Adrenal cortex - Adrenocortical tumor - Angiotensin II receptor - AT1 receptor - AT2
receptor - Aldosterone
