Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Department of Clinical Laboratory, Takeda General Hospital, Aizu-wakamatsu, Fukushima 965-8585, Japan.
Peptides. 2013 Nov;49:68-73. doi: 10.1016/j.peptides.2013.08.022. Epub 2013 Sep 8.
(Pro)renin receptor ((P)RR) is a specific receptor for renin and prorenin. The aim of the present study is to clarify expression and possible pathophysiological roles of (P)RR in aldosterone-producing adenomas (APAs) and other adrenal tumors. Expression of (P)RR was studied by immunocytochemistry, western blot analysis and real-time RT-PCR in adrenal tumor tissues obtained at surgery. Immunocytochemistry showed that (P)RR was expressed in normal adrenal glands and tumor tissues of adrenocortical tumors including APAs. In the normal adrenal glands, positive (P)RR immunostaining was observed in both adrenal cortex and medulla, with higher (P)RR immunostaining observed in zona glomerulosa and zona reticularis. Positive (P)RR immunostaining was also observed in the adrenocortical tumors, with elevated (P)RR immunostaining found in APAs, particularly in compact cells. By contrast, no apparent (P)RR immunostaining was observed in pheochromocytomas. Western blot analysis showed a band of (P)RR protein in normal adrenal glands and adrenocortical tumors at the position of 35 kDa. The relative expression levels of (P)RR protein were higher in tumor tissues of APAs than in attached non-neoplastic adrenal tissues of APAs. Real-time RT-PCR showed that expression levels of (P)RR mRNA were significantly increased in tumor tissues of APAs compared with other adrenal tumor tissues and attached non-neoplastic adrenal tissues of APAs. The present study has shown for the first time that expression of (P)RR is elevated in tumor tissues of APAs, raising the possibility that (P)RR may play pathophysiological roles in APAs, such as aldosterone secretion and cell proliferation.
(前)肾素受体((P)RR)是肾素和前肾素的特异性受体。本研究旨在阐明(P)RR 在醛固酮瘤(APA)和其他肾上腺肿瘤中的表达及其可能的病理生理作用。通过免疫细胞化学、Western blot 分析和实时 RT-PCR 研究了手术获得的肾上腺肿瘤组织中的(P)RR 表达。免疫细胞化学显示(P)RR 在正常肾上腺和包括 APA 在内的肾上腺皮质肿瘤的肿瘤组织中表达。在正常肾上腺中,(P)RR 免疫染色在肾上腺皮质和髓质中均为阳性,在肾小球带和网状带中(P)RR 免疫染色较高。(P)RR 免疫染色也见于肾上腺皮质肿瘤,在 APA 中发现(P)RR 免疫染色升高,尤其是在致密细胞中。相比之下,嗜铬细胞瘤中未见明显的(P)RR 免疫染色。Western blot 分析显示,正常肾上腺和肾上腺皮质肿瘤中有 35 kDa 处的(P)RR 蛋白带。APA 肿瘤组织中(P)RR 蛋白的相对表达水平高于 APA 附接的非肿瘤性肾上腺组织。实时 RT-PCR 显示,APA 肿瘤组织中(P)RR mRNA 的表达水平明显高于其他肾上腺肿瘤组织和 APA 附接的非肿瘤性肾上腺组织。本研究首次表明(P)RR 在 APA 肿瘤组织中表达升高,提示(P)RR 可能在 APA 中发挥病理生理作用,如醛固酮分泌和细胞增殖。