Differentially Expressed Mirnas in Zona Reticularis (ZR) Cells of the Human Adrenal Cortex

FRANCISCO GARCIA; DIEGO COLMAN; LUCIANA ZOFF; NORA ISABEL SARACO; ALICIA BELGOROSKY; MARIA SONIA BAQUEDANO

Congreso; Endo 2020; 2020

The human adrenal cortex, involved in adaptiveresponses to stress, fluid homeostasis, and secondarysexual characteristics, arises from a tightly regulateddevelopment of a zone and cell type-specific secretorypattern. However, the molecular mechanisms governingadrenal zonation, particularly postnatal ZR development,which produces adrenal androgens in a life-time-specificmanner, remain poorly understood. The hallmark of ZR isthe low expression of type 2 3β-hydroxysteroid dehydrogenase(HSD3B2). However, the mechanisms underlyingHSD3B2 downregulation in the ZR remain unknown.MiRNAs are seen as regulators of cell phenotypes. Theobjective of the study was to compare miRNA expressionprofiles in human adrenal ZR and zona fasciculata (ZF).ZF and ZR were microdissected from human adrenalstissues (n=5, from boys aged 16, 17 and 19 yr and girlsaged 12 and 16 yr) by laser capture microdissection(LCM). Total RNA was extracted from 5 ZF/ZR pairsand next-generation sequencing (NGS) was used to performthe microRNA expression profiling. 281 maturemicroRNAs were identified in human adrenal cortex.Among them, 7 microRNAs were significantly differentiallyexpressed between ZF and ZR. The expression ofmiR-375-3p, miR-483-3p and miR-7-5p was higher in ZRcompared with its paired ZF by 2-fold or greater. Multipleavailable bioinformatic algorithms (TargetScan, mi-Randa, DianaLab and PicTar) were employed to searchfor its target genes. Among predicted target genes, severalgenes (GATA-6, GATA-4, SF1, NR4A2, and IGF-1) are known to be involved in HSD3B2 regulation. Insummary, LCM combined with NGS provided a robustapproach to explore the adrenal zone-specific micro-RNAprofiling. Our data gave first hints that miRNAs might benovel regulatory modules associated with human adrenalZR cell-specific transcript regulation underlying developmentalandrogen production.