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Angiotensin II type 1 receptor and ACTH receptor expression in human adrenocortical neoplasms
B Schubert1, M Fassnacht, F Beuschlein
1Schwerpunkt Endokrinologie, Department of Medicine, University of Würzburg, Germany.
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 alpha32P-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 125I-Sar1, Ile8-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.
Insights
Angiotensin II type 1 receptor (AT1R) and ACTH receptor expression correlate with adrenal tumor function. AT1R is the primary receptor in these tumors, suggesting shared regulatory factors.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Type 1 angiotensin II (Ang II) receptors mediate key adrenal functions like steroidogenesis.
- Understanding Ang II receptor regulation in adrenal neoplasms is crucial.
Purpose of the Study:
- Investigate type 1 Ang II receptor expression in adrenocortical tissues.
- Define its regulation in adrenocortical neoplasms.
- Compare its expression with the ACTH receptor (ACTH-R).
Main Methods:
- Extracted Poly A RNA from tumor tissue for Northern blot analysis.
- Performed receptor autoradiography using radiolabeled Ang II and a selective antagonist.
- Analyzed expression in normal adrenals, cortisol-producing adenomas (CPA), aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), and carcinomas.
Main Results:
- Ang II type 1 receptor mRNA was significantly elevated in CPA and APA compared to normal adrenals, but low in NFA.
- ACTH receptor mRNA showed a similar pattern, with high expression in CPA and APA, and low/absent in NFA.
- A significant positive correlation (r = 0.692, P = 0.0019) was observed between Ang II type 1 receptor and ACTH-R mRNA levels.
- Autoradiography confirmed predominant type 1 Ang II receptor expression in tumor tissues, mainly in the zona glomerulosa of normal adrenals.
Conclusions:
- Ang II type 1 receptor and ACTH receptor expression are linked to the functional status of adrenocortical tumors.
- Similar regulatory factors may control the expression of both receptors.
- Type 1 Ang II receptor is the predominant subtype expressed in adrenocortical tumors, with minimal type 2 expression.