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Extracellular Vesicles and the New Endocrine Frontier

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The field of Endocrinology is a vast and exciting enterprise that encompasses nearly all branches of biology and medicine. Whether the focus is on development, reproduction, metabolism, immune function, aging or any other bodily process, the maintenance of homeostasis – and hence health – is vitally dependent ...

The field of Endocrinology is a vast and exciting enterprise that encompasses nearly all branches of biology and medicine. Whether the focus is on development, reproduction, metabolism, immune function, aging or any other bodily process, the maintenance of homeostasis – and hence health – is vitally dependent on the proper integration of hormonal signals emanating from various tissues. For much of the past 100 years, endocrine signals were considered to be primary form of long distance intercellular communication, involving hormonal transport in the blood either bound to plasma proteins or in a free, unbound state. Once delivered to specific surface or intracellular target receptors, hormones regulate both positively and negatively biological processes, such as gene expression, metabolic activity, channel function, and receptor signaling in target cells.

The traditional view of endocrine signaling as the primary regulator of distant tissue functions (in addition to nervous system or immune system control of many of the same tissues) has had to face a new reality in the past few years, as recently expanding research has begun to understand a third mode of intercellular communication, extracellular vesicles. Extracellular vesicles are membrane-bound vesicles derived either from budding of the plasma membrane (“microvesicles”) or inward budding of late endosomes, which generate multi-vesicular bodies that release “exosomes” into the extracellular environment of most tissues (Johnstone RM et al. 1987). Apoptotic vesicles are also included in the category of extracellular vesicles. Extracellular vesicles have been shown to contain functional proteins, lipids, DNA and microRNAs that reflect their specific tissue origins. Importantly, extracellular vesicles (EVs) typically express surface proteins of various forms that promote interaction with distant recipient cells, usually involving delivery of the EV contents into the target cells (Thery et al 2009; Record et al 2011; Hoshino et al. 2015).

These new discoveries have understandably had considerable impact on the field of endocrine research. Some of the earlier findings include exosome microRNA profiling in diabetes (Santovito D et al. 2014), exosomes and follicular maturation (da Silveira JC et al 2014), exosomal microRNAs and breast, thyroid and prostate cancers (Chen WX et al 2014; Lee JC et al 2015; Huang X et al 2015), and many others. This burgeoning research over the past few years is testament to a hugely exciting frontier for systems and translational endocrinology. Among the important ramifications of EVs in endocrinology are 1) novel insights into the molecular regulation of cellular physiology, 2) highly tissue-specific biomarkers of real-time EV secretion, and hence, assessment of tissue state under various conditions of health and disease, and 3) new therapeutic tools for delivery of bioactive molecules in a cell-specific targeted manner. The need for more research into the biological processes governing EV release, the roles of secreted vesicles in cell-cell communication, and the potential biomedical utility of EV is warranted. Advancements in our understanding of EVs as a novel mode of intercellular interactions will most certainly contribute to new diagnostic and treatment strategies for improving medical care and human well-being.


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