The investigation of expression and functional relevance of G-protein coupled receptors in primary aldosteronism (PA) by molecular and clinical studies.
Patients and methods
Tissues of 14 aldosterone-producing adenomas (APA), of one unilateral adrenal hyperplasia and of six healthy adult adrenal glands; 12 patients with confirmed PA due to APA; (n=5), idiopathic hyperaldosteronism (n=7) and 8 control subjects (C). The tissues were subjected to a quantitative PCR for determination of mRNA expression levels of AT2R1, GIPR, MC2R, GnRHR, LHR, TRHR, TSHR, glucagon-R, V1aR, V2R, and 5-HT4R. The patients and controls were enrolled in a test protocol consisting of stimulation by posture, mixed meal, ACTH, GnRH, TRH, glucagon, vasopressin, and metoclopramide (MCP). Three patients could be analyzed by both studies. A positive response was defined as an aldosterone increase of more than 50% following stimulation.
All the tissues revealed AT2R1, MC2R, AVPR, and 5-HT4R mRNA expression. LHR mRNA was found in normal adrenals and 13 adrenal tumors. By contrast with normal adrenals tumorous adrenal tissue expressed GnRHR mRNA (4/15) and TSHR mRNA (1/15). Both the patients and controls responded to posture, ACTH, glucagon, AVP, and MCP. Specific responses were seen in one patient following TRH and three patients following GnRH stimulation.
We provide evidence for peptide hormone responsiveness to various peptide hormones in patients with PA, including GnRH and TRH. A good correlation between clinical and molecular testing could be observed, making an involvement of the receptor expressed in PA possible.