What is it about?

Extracellular vesicles (EVs), which are tiny membrane-bound structures produced by cells, circulate in the blood at concentrations approximately one billion per milliliter. EVs are known to affect target cells directly, by interacting with hormones (which are proteins), or through endocrine cells. We studied how EVs interact with an important prohormone, proopiomelanocortin (POMC), in the blood before and after physical exercise. POMC can be processed into several active hormones: a stress hormone (adrenocorticotropic hormone, ACTH), a group of hormones involved in skin pigmentation, immune function, appetite regulation, and energy balance (melanocyte-stimulating hormones, MSH) and hormones associated with exercise, pain relief, and human behaviors (beta-endorphins).

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Why is it important?

We found a previously unknown mechanism by which EVs and a hormone can interact. The POMC bound to special proteins called receptors on the surface of the EVs. Association of the POMC with EVs increased transport of the POMC across a model of the blood brain barrier. We also discovered that exercise increased association between POMC and EVs, which is a new insight into how exercise could change hormone circulation in the body.

Perspectives

This started as a simple student project to understand if beta-endorphin associated with EVs during exercise. It turned into an example of following the data into new discoveries with the help of an open-minded team of experts from different disciplines on two continents. Because it uncovered new ways for EVs and hormones to interact, my hope is that this discovery can improve understanding of hormone circulation, drug delivery, and exercise effectiveness.

Aurelio Lorico

The discovery that the (pro)hormone associates with extracellular vesicles fundamentally reshapes our understanding of hormone circulation and highlights promising opportunities for regenerative medicine and targeted drug delivery, particularly for applications in the brain.

Denis Corbeil
Technische Universitat Dresden

It has been fun to discover this interesting story with such a multi-talented team of scientists! There are several lifetimes of potential projects that coud grow out of this work.

Cheryl Hightower
Imgen Research Group

Read the Original

This page is a summary of: Physical exercise increases binding of POMC to blood extracellular vesicles, Proceedings of the National Academy of Sciences, December 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2525044122.
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