GATA6, SF1, NGFIB and DAX1 in the remodeled subcapsular zones in primary aldosteronism

Endocr J. 2014;61(4):393-401. doi: 10.1507/endocrj.ej13-0103. Epub 2014 Feb 15.

Abstract

The majority of the cases diagnosed as primary aldosteronism (PA) are caused by aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). Histopathologically, both IHA and adjacent adrenal glands of APA demonstrate remodeled subcapsular zone (RSZ) but these zones in two disorders are markedly different in terms of steroidogenesis. 3β-Hydroxysteroid dehydrogenase/Δ⁵-Δ⁴ isomerase (3β-HSD) expression has been known to be activated synergistically by GATA6 and SF1, and repressed by DAX1 through abolishing the activation. Nerve growth factor-induced clone B (NGFIB) is also known as one of the transcription factors to bind to and activate 3β-HSD promoter. The results of our immunohistochemical analysis demonstrated the expression levels of 3β-HSD in RSZ of IHA were higher than in RSZ of adjacent adrenals of APA, while those in the zona glomerulosa (ZG) of normal adrenal gland (NA) were in between these two RSZs. The expression levels of GATA6, SF1 and DAX1 did not prominently differ among these three types of adrenals, especially between in RSZs of IHA and APA cases, indicating the marked difference of 3β-HSD expression was unlikely to be explained by the levels of these three factors. However, the levels of NGFIB expression were significantly higher in RSZ of IHA than in RSZ of adjacent adrenals of APA and the ZG of NA (P<0.05), which may partly account for the expression levels of 3β-HSD among the three groups of adrenals. These results may imply NGFIB plays important roles in the marked differences in steroidogenic functions in the two distinct types of RSZ of PA cases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / pathology
  • Adrenal Cortex Neoplasms / physiopathology
  • Adrenal Cortex Neoplasms / surgery
  • Adrenocortical Adenoma / metabolism
  • Adrenocortical Adenoma / pathology
  • Adrenocortical Adenoma / physiopathology
  • Adrenocortical Adenoma / surgery
  • Biomarkers / metabolism
  • DAX-1 Orphan Nuclear Receptor / metabolism*
  • Down-Regulation
  • GATA6 Transcription Factor / metabolism*
  • Humans
  • Hyperaldosteronism / etiology
  • Hyperaldosteronism / metabolism*
  • Hyperaldosteronism / pathology
  • Hyperaldosteronism / surgery
  • Immunohistochemistry
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Steroidogenic Factor 1 / metabolism*
  • Up-Regulation*
  • Zona Glomerulosa / metabolism*
  • Zona Glomerulosa / pathology
  • Zona Glomerulosa / surgery

Substances

  • Biomarkers
  • DAX-1 Orphan Nuclear Receptor
  • GATA6 Transcription Factor
  • GATA6 protein, human
  • NR0B1 protein, human
  • NR4A1 protein, human
  • NR5A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Steroidogenic Factor 1
  • 3-Hydroxysteroid Dehydrogenases