Expression of Type-1 Angiotensin-ii Receptors In Human Aldosteronomas

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 ATI 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. ATI mRNA (similar to 2.4 kb) was expressed in all the aldosteronomas tested. Densitometric analysis of AT1 signals, corrected by beta actin expression, when compared to nontumorous 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. I-125-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 ATI gene and the formation of an apparently normal receptor suggest that AT1 receptor should have a role in aldosteronoma cell biology.