title: Isoform-specific monoclonal antibodies against 3β-hydroxysteroid dehydrogenase/isomerase family provide markers for subclassification of human primary aldosteronism.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Systems Biology (M.D., J.-M.F., M.T., Y.H., Y.T., H.O.), Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; and Departments of Medicine (F.S., R.M., S.I.), Pathology (T.M., Y.N., H.S.), and Radiology (K.T.), Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai 980-8574, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Fustin
authors.forename: Motomi
authors.initials: M
authors.lastname: Tainaka
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Hotta
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Kei
authors.initials: K
authors.lastname: Takase
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000276:immunology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000302:Adrenal Cortex / Q000378:metabolism* / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D006801:Humans; D006929:Hyperaldosteronism / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D015384:Zona Glomerulosa / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015096:3-Hydroxysteroid Dehydrogenases