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Angiotensin II type 1 receptor and ACTH receptor expression in human adrenocortical neoplasms
Author(s) -
Schubert Barbara,
Fassnacht Martin,
Beuschlein Felix,
Zenkert Simone,
Allolio Bruno,
Reincke Martin
Publication year - 2001
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2001.01253.x
Subject(s) - endocrinology , medicine , acth receptor , receptor , angiotensin ii , zona glomerulosa , adrenal cortex , losartan , aldosterone , biology , adrenocortical carcinoma , adrenocorticotropic hormone , chemistry , hormone
OBJECTIVE Type 1 angiotensin II (Ang II) receptors transduce most of the known actions of Ang II, including steroidogenesis and trophic actions on the adrenal cortex. We investigated the type 1 Ang II receptor expression in adrenocortical tissues to define its regulation in adrenocortical neoplasms and to compare its expression with that of the ACTH receptor (ACTH‐R). PATIENTS AND MEASUREMENTS Poly A RNA was extracted from tumour tissue and electrophoresed through a 1·0% agarose gel, blotted and hybridized with α 32 P‐CTP labelled PCR generated type 1 Ang II receptor cDNA probe. Receptor autoradiography was performed on slices from normal adrenals and tumour tissue by incubation with 125 I‐Sar 1 , Ile 8 ‐Ang II with and without pretreatment with cold Ang II or with the selective type 1 receptor antagonist losartan. RESULTS Ang II type 1 receptor mRNA was high in cortisol producing (CPA; n = 5) and aldosterone producing (APA; n = 4) adenomas (normal adrenals 100 ± 12% vs. 180 ± 16% in CPA and 154 ± 26% in APA, mean ± SEM), but was low in nonfunctioning adenomas (NFA; n = 2; 2 ± 1%). ACTH receptor mRNA followed a similar pattern (CPA 178 ± 17, APA 196 ± 30, NFA 0%, carcinomas 56 ± 11%) with a good correlation between Ang II type 1 receptor and ACTH‐R mRNA of r = 0·692, P = 0·0019. Receptor autoradiography in normal adrenals demonstrated Ang II type 1 receptors predominantly in the zona glomerulosa. In tumour tissue, mainly type 1 receptor expression was found confirming the Northern blot data. CONCLUSIONS Angiotensin II type 1 receptor and ACTH receptor expression seems to be correlated with the functional status of adrenocortical tumours, suggesting regulation by similar factors. The predominant receptor expressed in adrenocortical tumours is the Angiotensin II type 1 receptor whereas type 2 receptor expression is minimal.