DNA methylation is not involved in specific down-regulation of HSD3B2, NR4A1 and RARB genes in androgen-secreting cells of human adrenal cortex

Mol Cell Endocrinol. 2017 Feb 5:441:46-54. doi: 10.1016/j.mce.2016.09.024. Epub 2016 Sep 23.

Abstract

We hypothesized that DNA methylation is involved in human adrenal functional zonation. mRNAs expression and methylation pattern of RARB, NR4A1 and HSD3B2 genes in human adrenal tissues (HAT) and in pediatric virilizing adrenocortical tumors (VAT) were analyzed. For analysis of the results samples were divided into 3 age groups according to FeZ involution, pre and post-adrenarche ages. In all HAT, similar RARB mRNA was found including microdissected zona reticularis (ZR) and zona fasciculata, but HSD3B2 and NR4A1 mRNAs were lower in ZR (p < 0.05). NR4A1 and RARB promoters remained unmethylated in HAT and VAT. No adrenal zone-specific differences in NR4A1 methylation were observed. In summary, RARB was not associated with ZR-specific downregulation of HSD3B2 in postnatal human adrenocotical zonation. DNA methylation would not be involved in NR4A1 adrenocortical cell-type specific downregulation. Lack of CpG islands in HSD3B2 suggested that HSD3B2 ZR-specific downregulation would not be directly mediated by DNA methylation.

Keywords: Adrenal zonation; DNA methylation; HSD3B2; NR4A1; RARB.

MeSH terms

  • Adolescent
  • Adrenal Cortex / cytology*
  • Adrenal Cortex Neoplasms / genetics
  • Androgens / metabolism*
  • Child
  • Child, Preschool
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Down-Regulation*
  • Gene Expression Regulation
  • Humans
  • Infant
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • Progesterone Reductase / genetics*
  • Progesterone Reductase / metabolism
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / metabolism
  • Young Adult

Substances

  • Androgens
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • retinoic acid receptor beta
  • 3 beta-hydroxysteroid dehydrogenase type II
  • Progesterone Reductase