QUANTITATIVE-ANALYSIS OF MESSENGER-RIBONUCLEIC-ACID ENCODING NATRIURETIC PEPTIDE RECEPTORS IN ALDOSTERONE-PRODUCING ADENOMA

There exist conflicting data regarding the inhibitory effect of atrial natriuretic peptide on aldosterone production from aldosterone-producing adenoma (APA). Natriuretic peptides mediate their actions through natriuretic peptide receptors (NPRs). Whether or not NPRs are present in the tumors remains controversial. To elucidate this paradox, gene expression of NPRs was examined by Northern blot analysis and competitive polymerase chain reaction in tumorous and non-tumorous portions of APA, and in normal adrenal gland from patients with renal cell carcinoma. The results of Northern blot analysis showed the presence of messenger ribonucleic acid (mRNA) of three NPRs in all adrenal tissues, including APA. The proportional expression of NPR gene transcripts in APA was type A (0.6%), type B (18.7%), and type C (80.7%). The levels, but not the proportions, of type C and possibly type B NPR mRNAs were lower in tumorous and non-tumorous portions of APA compared to those in normal adrenal gland (type C 190.2 +/- 24.5 [means +/- SEM, normal adrenal gland] > 168.1 +/- 20.8 [non-tumorous portion] > 112.2 +/- 15.5 [tumorous portion] pg/10 mu g total RNA, F = 3.82, P < 0.05; type B 45.2 +/- 8.5 [normal adrenal gland] > 30.0 +/- 5.2 [non-tumorous portion] > 25.1 +/- 4.1 [tumorous portion] pg/10 mu g total RNA, F = 3.03, P = 0.065). The mRNA levels of type C, rather than type A or type B, NPR were correlated with the percentage of zona fasciculata-like cells in APA (r = 0.90, P < 0.05). In conclusion we have demonstrated the presence of mRNA encoding the three NPRs in APA, By quantitative analysis, the proportional expression of the three subtypes is not different between APA and adrenal glands, with type C NPR being the most abundant, followed by type B and type A. Type C and possibly type B NPR gene transcripts were downregulated in both tumorous and non-tumorous portions of APA. The gene expression of GC-coupled NPRs of APA is not histologically dependent.