EXPRESSION OF TYPE-1 ANGIOTENSIN-II RECEPTORS IN HUMAN ALDOSTERONOMAS

Type 1 angiotensin II (AII) receptors (AT1 receptors), besides stimula tion of aldosterone secretion, seem to transduce the growth factor-lik e activity of AII on glomerulosa cells. Although a local renin-angiote nsin system and AII synthesis have been found in human adrenals and al dosteronomas, it is unclear whether aldosteronomas express ATI recepto rs. Utilizing polymerase chain reaction (PCR) and reverse transcriptio n-PCR (RT-PCR) with primers complementary to both genomic and cDNA seq uences of human AT1 receptor, we have amplified and cloned a 734 bp fr agment of the AT1 coding region. This DNA, after cloning and sequencin g, was used for Northern analysis. Total RNA was extracted from 5 non- tumorous adrenals and 5 aldosteronomas. ATI mRNA (similar to 2.4 kb) w as expressed in all the aldosteronomas tested. Densitometric analysis of AT1 signals, corrected by beta actin expression, when compared to n ontumorous adrenals, did not show significant differences. AT1 recepto r density and affinity in cell membrane obtained from 9 non-tumorous a drenal cortex and 8 aldosteronomas were also studied. I-125-AII was us ed as ligand and Dup 753 as AT1 antagonist: AT1 receptor density and a ffinity were not Significantly different in aldosteronomas vs non-tumo rous 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.