Gene Expression and Roles of Angiotensin II Type 1 and Type 2 Receptors in Human Adrenals

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