The role of miRNAs in regulating adrenal and gonadal steroidogenesis

Abstract

miRNAs are endogenous noncoding single-stranded small RNAs of ~22 nucleotides in length that post-transcriptionally repress the expression of their various target genes. They contribute to the regulation of a variety of physiologic processes including embryonic development, differentiation and proliferation, apoptosis, metabolism, hemostasis and inflammation. In addition, aberrant miRNA expression is implicated in the pathogenesis of numerous diseases including cancer, hepatitis, cardiovascular diseases and metabolic diseases. Steroid hormones regulate virtually every aspect of metabolism, and acute and chronic steroid hormone biosynthesis is primarily regulated by tissue-specific trophic hormones involving transcriptional and translational events. In addition, it is becoming increasingly clear that steroidogenic pathways are also subject to post-transcriptional and post-translational regulations including processes such as phosphorylation/dephosphorylation, protein‒protein interactions and regulation by specific miRNAs, although the latter is in its infancy state. Here, we summarize the recent advances in miRNA-mediated regulation of steroidogenesis with emphasis on adrenal and gonadal steroidogenesis.

HIF1α is an essential regulator of steroidogenesis in the adrenal gland

“…However, our findings that HIF1α deletion results in the upregulation of mRNA of a vast majority of steroid-related enzymes is counterintuitive to the nature of this transcription factor (12, 51), and therefore we believe this effect is most likely indirect with potential involvement of one or more transcriptional repressors (13,52,53). This type of transcriptional regulation of adrenal steroidogenesis has already been suggested with miRNAs, which are endogenous noncoding single-stranded small RNAs that suppress the expression of various target genes (54 Glucocorticoids and aldosterone are both essential for homeostasis and their substantial increase in P2H1 mice was intriguing, given their pivotal role in immune suppression (3,58) and blood pressure regulation, respectively. Previous studies have shown that aldosterone not only increases the expression of the potassium channels that secrete potassium but also stimulates K-absorptive pumps in the renal cortex and medulla, thereby stabilizing and maintaining renal potassium excretion (59), a situation we also observed in the P2H1 mice.…”

The Roles of the miRNAome and Transcriptome in the Ovine Ovary Reveal Poor Efficiency in Juvenile Superovulation

“…In this study, miR-145-x and miR-144-y were also highly expressed and were down- and upregulated, respectively, in the lamb libraries. In addition, downregulation of the miRNAs oar-miR-10a and miR-145-x in lambs was speculated in the present study, implicating suppression of granulosa cell proliferation by the targeting of brain-derived neurotropic factor ( BDNF ) and activin receptor IB ( ACVRIB ) [ 7 , 46 , 47 ].…”

“…The miRNAs are a class of highly conserved small non-coding RNAs that can modulate mRNA and protein expression [ 6 ]. It has been proven that miRNAs participate in various physiological processes, including hormone secretion [ 7 ], organogenesis [ 8 ], cell proliferation [ 9 ], apoptosis [ 10 ], differentiation [ 11 ], metabolism [ 12 ], and reproduction control [ 13 ]. It has been estimated that miRNAs, which occupy a very small proportion of predicted genomes, could regulate up to one-third of all protein-coding genes in higher eukaryotes [ 14 ].…”

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids—From Bench to Bedside

“…According to the recently accumulated data, miRNAs are commonly predicted to target genes responsible for ovarian steroid receptors, TGF-β and its receptors and several inflammation-derived genes [29,35,64]. The regulatory functions of miRNAs in inflammation are critical for the initiation and termination of these processes [65,66].…”