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Mol Cell Endocrinol. 2015 Jun 15;408:205-12. doi: 10.1016/j.mce.2014.10.008. Epub 2014 Oct 22.

3β-Hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma.

Author information

1
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Japan.
3
Tohoku University School of Medicine, Sendai, Japan.
4
Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
5
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.
6
Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS, USA; Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.
7
Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
8
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: hsasano@patholo2.med.tohoku.ac.jp.

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.

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)

PMID:
25458695
PMCID:
PMC4821076
DOI:
10.1016/j.mce.2014.10.008
[Indexed for MEDLINE]
Free PMC Article

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