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

Abstract

We hypothesized that DNA methylation is involved in human adrenal functional zonation. mRNAsexpression 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 sampleswere 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, butHSD3B2 and NR4A1 mRNAs were lower in ZR (p < 0.05). NR4A1 and RARB promoters remainedunmethylated in HAT and VAT. No adrenal zone-specific differences in NR4A1 methylation wereobserved.In summary, RARB was not associated with ZR-specific downregulation of HSD3B2 in postnatal humanadrenocotical zonation. DNA methylation would not be involved in NR4A1 adrenocortical cell-typespecific downregulation. Lack of CpG islands in HSD3B2 suggested that HSD3B2 ZR-specific downregulationwould not be directly mediated by DNA methylation.