Endocrine Abstracts

The capacity of microRNAs (miRNAs) to simultaneously repress multiple targets provide a mechanism to treat disease by modulating entire biological networks. miRNAs are present in the systemic circulation and other biological fluids associated with extracellular microvesicles, exosomes, Ago2 complex or HDL. Even exogenous miRNAs have been described in our circulation. The active secretion of miRNAs by the cells has been suggested to mediate intercellular communication. The inter-organ and intra-organ cross-talk, traditionally mediated by hormones, was recently evidenced to be also regulated by extracellular vesicles. However, the biological significance, the factors that modulate their extracellular secretion and the mechanisms by which they reach the target tissue still remains elusive. Exosomes are stable nanovesicles that transport bioactive molecules (i.e. miRNAs) to target cells. One of the advantages of exosomes is that they can easily cross the blood-brain barrier without use of an additive vehicle. Recent evidence suggest that breast milk exosomes contain miRNAs that can be transferred from mother to infants, producing a potential inter-individual communication via miRNAs. Moreover, increasing evidence suggest that exogenous miRNAs can be transferred from diet (i.e. plants-derived miRNAs) and taken up by mammalian cells where they exert a biological effect. Their transport in extracellular vesicles might avoid their degradation by extracellular/intracellular RNases, being active signaling molecules involved in the intercellular communication. However, their real in vivo biological effects are under debate. In addition, how much extracellular miRNAs reach the target cell to exert a hormone-like effects is poorly understood. We here discuss some relevant biological process to understand the potential of extracellular miRNAs as hormones. The many barriers when reaching the circulatory system, the biological barriers before entering any target-cells and bypass the many intracellular barrier to reach the appropriate subcellular localization in order to exert any effects is also point out.