Expression of type 1 angiotensin II receptors in human aldosteronomas

Abstract

Type 1 angiotensin II (AII) receptors (AT1 receptors), besides stimulation of aldosterone secretion, seem to transduce the growth factor-like activity of AII on glomerulosa cells. Although a local renin-angiotensin system and AII synthesis have been found in human adrenals and aldosteronomas, it is unclear whether aldosteronomas express AT1 receptors. Utilizing polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) with primers complementary to both genomic and cDNA sequences of human AT1 receptor, we have amplified and cloned a 734 bp fragment of the AT1 coding region. This DNA, after cloning and sequencing, was used for Northern analysis. Total RNA was extracted from 5 non-tumorous adrenals and 5 aldosteronomas. AT1 mRNA (∼ 2.4 kb) was expressed in all the aldosteronomas tested. Densitometric analysis of AT1 signals, corrected by β actin expression, when compared to non-tumorous adrenals, did not show significant differences. AT1 receptor density and affinity in cell membrane obtained from 9 non-tumorous adrenal cortex and 8 aldosteronomas were also studied. ¹²⁵I-AII was used as ligand and Dup 753 as AT1 antagonist: AT1 receptor density and affinity were not significantly different in aldosteronomas vs non-tumorous adrenal cortex. In conclusion, the expression of AT1 gene and the formation of an apparently normal receptor suggest that AT1 receptor should have a role in aldosteronoma cell biology.