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The blood–brain barrier as an endocrine tissue

Abstract

The blood–brain barrier (BBB) was first noted for its ability to prevent the unregulated exchange of substances between the blood and the central nervous system (CNS). Over time, its characterization as an interface that enables regulated exchanges between the CNS and substances that are carried in the blood in a hormone-like fashion have emerged. Therefore, communication between the CNS, BBB and peripheral tissues has many endocrine-like properties. In this Review, I examine the various ways in which the BBB exhibits endocrine-related properties. The BBB is a target for hormones, such as leptin and insulin, that affect many of its functions. The BBB is also a secretory body, releasing substances either into the blood or the interstitial fluid of the brain. The BBB selectively allows classical and non-classical hormones entry to and exit from the CNS, thus allowing the CNS to be both an endocrine target and a secretory tissue. The BBB is affected by endocrine diseases such as diabetes mellitus and can cause or participate in endocrine diseases, including those related to thyroid hormones and obesity. The endocrine-like mechanisms of the BBB can extend the definition of endocrine disease to include neurodegenerative conditions, including Alzheimer disease, and of hormones to include cytokines, triglycerides and fatty acids.

Key points

  • The blood–brain barrier (BBB) acts as both a secretory and target endocrine tissue.

  • By regulating the transport of hormones into and out of the brain, the BBB provides a mechanism by which the central nervous system can act as an endocrine secretory and target tissue.

  • The BBB facilitates substances not typically thought of as hormones acting in an endocrine-like fashion, including triglycerides, short-chain fatty acids and lipopolysaccharide.

  • BBB function can be altered in endocrine diseases either because of adaptions to the disease condition or because it is a disease target.

  • BBB dysfunction or impairment can cause or promote the progression of endocrine or metabolic diseases.

  • The BBB is an important factor in the treatment of many diseases, often as a therapeutic target or as a barrier that must be negotiated.

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Fig. 1: The presence and architecture of tight junctions results in polarization of the brain endothelial cell.
Fig. 2: The vascular blood–brain barrier as an endocrine tissue.
Fig. 3: Blood-to-brain transport of leptin into the arcuate nucleus: integration of signals and changes with feeding state.

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Nature Reviews Endocrinology thanks B. Levin, D. Begley and V. Prevot, and the other anonymous reviewers, for their contribution to the peer review of this work.

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Glossary

Neurovascular unit

A multicellular and multicomponent network that is composed of neurons, glial cells, brain endothelial cells and extracellular matrix components. The neurovascular unit is key to neurovascular coupling and to the delivery of key nutrients and oxygen from the circulatory system into the brain.

Plasma protein binding

The degree to which a substance binds to proteins within the blood.

Choroid plexus

The choroid plexus, which consists of modified ependymal cells, produces the cerebrospinal fluid in the ventricles of the brain.

Allan–Herndon–Dudley syndrome

A condition resulting from deficient thyroid hormone transport across the blood–brain barrier characterized by cognitive impairment, lack of speech and hypotonia.

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Banks, W.A. The blood–brain barrier as an endocrine tissue. Nat Rev Endocrinol 15, 444–455 (2019). https://doi.org/10.1038/s41574-019-0213-7

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