The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. Scientists from the University of Glasgow previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. In a recent study, they assess microRNA regulation across the whole corticosteroid pathway using miRNA microarray technology.

Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different.

This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature.

LC Sciences

H295R cells transfected with miR-320a-3p Pre-miR, miR-320a-3p Anti-miR, or with a scrambled negative control RNA. CYP11A1 (a) or CYP17A1 (b) mRNA was measured 48 hours posttransfection by qRT-PCR, with cycle threshold values normalised to β-actin mRNA and expressed relative to negative control. Results represent the mean of three independent biological experiments performed in triplicate ± SEM.

 

Reference
S. Robertson, L. A. Diver, S. A-M, C. Livie, E. Davies et al. (2017) Regulation of Corticosteroidogenic Genes by MicroRNA Int. J. of Endocrinol. doi: 10.1155/2017/2021903 [article]

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