Abstract
The (pro)renin receptor [(P)RR] is a multifunctioning protein playing roles in various pathological conditions. A soluble form of (P)RR [s(P)RR] has been considered a biomarker for (P)RR expression in tissues. Expression of (P)RR has been described in aldosterone-producing adenoma (APA), but the roles of (P)RR have yet to be fully determined. This study investigated the significance of (P)RR and serum s(P)RR concentrations in patients with APA. We evaluated associations between (P)RR expression and expression of CYP11B2, an aldosterone synthase, and aldosterone production by the adrenal glands and assessed the relationships between serum s(P)RR concentration and background factors. (P)RR colocalized with CYP11B2 and expression levels of (P)RR were positively associated with those of CYP11B2 in APA tissues. (P)RR immunoreactivity in these tissues correlated positively with plasma aldosterone concentrations (PAC) and urinary aldosterone excretion. Also, in APA, (P)RR mRNA abundance was positively correlated with β-catenin mRNA abundance. Significant positive correlations were identified between serum s(P)RR concentration and plasma glucose, hemoglobin A1c, and serum creatinine levels, but not with PAC (in either peripheral vein or adrenal vein) or adrenal (P)RR expression level. This study showed that (P)RR expression level correlates with CYP11B2 expression in APA tissues and PAC and urinary aldosterone excretion, suggesting that (P)RR expression may contribute to aldosterone synthesis via CYP11B2 activation in APAs, although serum s(P)RR concentration failed to show any significant relationship with adrenal (P)RR expression. Adrenal (P)RR activity might offer a therapeutic target in the treatment of PA, although this issue needs to be investigated in future studies.
Highlights
Primary aldosteronism (PA) was first described as a clinical syndrome characterized by hypokalemia, hypertension, and impaired glucose tolerance by Conn in 1955 [1]
PA is defined as autonomous aldosterone production leading to a downregulation of renin and is characterized by histological features including adrenal aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism. is pathology represents the most common endocrine form of secondary hypertension and its prevalence has been increasing recently. e incidence of cardiovascular morbidity is well known to be higher in patients with PA than in patients with essential hypertension [2]
Hormonal data revealed suppressed PRA and increased plasma aldosterone concentrations (PAC). ese laboratory data were compatible with PA due to APA
Summary
Primary aldosteronism (PA) was first described as a clinical syndrome characterized by hypokalemia, hypertension, and impaired glucose tolerance by Conn in 1955 [1]. Recent studies have demonstrated that both CYP11B2 expression in the tumor and tumor size contribute to the overproduction of aldosterone in APA, and CYP11B2 immunohistochemical staining is considered a useful. While Wnt signaling plays a crucial role in pattern formation during embryogenesis, previous reports have demonstrated that aberrant Wnt/β-catenin signaling is associated with APA development and controls aldosterone production [8]. PRA and PAC from venous blood samples were measured with the patient in a sitting position (for at least 15 min) at the first admission. Serum s(P)RR level was measured, in both peripheral and adrenal venous blood samples, using an enzyme-linked immunosorbent assay (ELISA) kit consisting of a solid-phase Sandwich ELISA with two kinds of highly specific antibody [19]. Serum s(P)RR level was measured, in both peripheral and adrenal venous blood samples, using an enzyme-linked immunosorbent assay (ELISA) kit consisting of a solid-phase Sandwich ELISA with two kinds of highly specific antibody [19]. e 24 h urine collection was obtained while the patients were consuming their usual diet and without changing their level of physical activity
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