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

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

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).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / enzymology*
  • Adenoma / genetics
  • Adenoma / pathology
  • Aldosterone / biosynthesis*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Progesterone Reductase / genetics
  • Progesterone Reductase / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Steroid Isomerases / genetics
  • Steroid Isomerases / metabolism*

Substances

  • 3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
  • Isoenzymes
  • Multienzyme Complexes
  • Aldosterone
  • 3 beta-hydroxysteroid dehydrogenase type II
  • Progesterone Reductase
  • Steroid Isomerases