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タイトル: Isoform-specific monoclonal antibodies against 3β-hydroxysteroid dehydrogenase/isomerase family provide markers for subclassification of human primary aldosteronism.
著者: Doi, Masao
Satoh, Fumitoshi
Maekawa, Takashi
Nakamura, Yasuhiro
Fustin, Jean-Michel
Tainaka, Motomi
Hotta, Yunhong
Takahashi, Yukari
Morimoto, Ryo
Takase, Kei
Ito, Sadayoshi
Sasano, Hironobu
Okamura, Hitoshi
著者名の別形: 土居, 雅夫
発行日: 19-Dec-2013
出版者: Endocrine Society
誌名: The Journal of clinical endocrinology and metabolism
巻: 99
号: 2
開始ページ: E257
終了ページ: E262
抄録: [Context]: Therapeutic management of primary aldosteronism requires accurate differentiation between aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). However, little is known about the molecular features that delineate the difference between APA and IHA. Two different isoforms of 3β-hydroxysteroid dehydrogenase (HSD3B1 and HSD3B2) are thought to be expressed in the human adrenal gland, but the lack of isoform-specific antibody has so far hampered mapping of these isoforms in APA and IHA. [Objectives]: The aim of our study is to develop and characterize isoform-specific monoclonal antibodies against HSD3B1 and HSD3B2. Using these antibodies, we determined for the first time the immunolocalization of HSD3B1 and HSD3B2 in normal human adrenal cortex as well as in adrenal specimens from APA and IHA. [Results]: Immunohistochemical analysis with isoform-specific antibodies revealed zone-specific expression of HSD3B1 and HSD3B2 in the adrenal cortex. HSD3B1 immunoreactivities were essentially confined to the zona glomerulosa (ZG), in which aldosterone is produced. In contrast, HSD3B2 was not confined to the ZG but was found across the zona fasciculata, which is where cortisol is produced. Moreover, immunohistopathological analysis of primary aldosteronism revealed a previously uncharacterized difference between APA and IHA. Notably, hyperplasia of ZG seen for IHA was accompanied by a robust expression of ZG isoform HSD3B1. In contrast, tumor cells in APA were not immunopositive to HSD3B1. Rather, a strong and dominant expression of HSD3B2 characterized APA. Moreover, perhaps due to compensatory responses to excess aldosterone, APA had an adjacent ZG whose immunoreactivities to HSD3B1 and HSD3B2 were profoundly reduced. [Conclusions]: Isoform-specific monoclonal antibodies against HSD3B1 and HSD3B2 may be of great value for immunohistochemical differentiation between APA and IHA.
著作権等: © 2014 by the Endocrine Society.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/197309
DOI(出版社版): 10.1210/jc.2013-3279
PubMed ID: 24423300
出現コレクション:学術雑誌掲載論文等

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