title: 3β-Hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma.
abstract: It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P <0.0001) and plasma aldosterone concentration (PAC) of the patients (P <0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P <0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P <0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Konosu-Fukaya
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Saulo J A
authors.initials: SJ
authors.lastname: Felizola
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Ise
authors.affiliation: Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Koshin
authors.initials: K
authors.lastname: Katsu
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasajima
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS, USA; Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Elise P
authors.initials: EP
authors.lastname: Gomez-Sanchez
authors.affiliation: Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS, USA; Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.affiliation: Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: hsasano@patholo2.med.tohoku.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000236:Adenoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000450:Aldosterone / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism*
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D007527:Isoenzymes; D009097:Multienzyme Complexes; D000450:Aldosterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D013251:Steroid Isomerases
keywords: 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1); 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2); Aldosterone-producing adenoma (APA); CYP11B1 (11β-hydroxylase) and KCNJ5; CYP11B2 (aldosterone synthase)