Abstract
Thyroid hormone (TH) transport into the brain is not only pivotal for development and differentiation, but also for maintenance and regulation of adult central nervous system (CNS) function. In this review, we highlight some key factors and structures regulating TH uptake and distribution. Serum TH binding proteins play a major role for the availability of TH since only free hormone concentrations may dictate cellular uptake. One of these proteins, transthyretin is also present in the cerebrospinal fluid (CSF) after being secreted by the choroid plexus. Entry routes into the brain like the blood–brain-barrier (BBB) and the blood–CSF-barrier will be explicated regarding fetal and adult status. Recently identified TH transmembrane transporters (THTT) like monocarboxylate transporter 8 (Mct8) play a major role in uptake of TH across the BBB but as well in transport between cells like astrocytes and neurons within the brain. Species differences in transporter expression will be presented and interference of TH transport by endogenous and exogenous compounds including endocrine disruptors and drugs will be discussed.
Highlights
Reviewed by: Takashi Yoshimura, Nagoya University, Japan Heike Heuer, Leibniz Institute for Age Research-Fritz Lipmann Institute, Germany
Transthyretin is present in the cerebrospinal fluid (CSF) after being secreted by the choroid plexus
T4 is locally metabolized by selenoenzymes to either active T3 via Type 2 deiodinase (Dio2) or inactivated by Type 3 deiodinase (Dio3), to yield reverse T3. rT3, devoid of T3-like action, might be involved in developmental regulation of neuronal migration guided by astrocytes and glial cells [1]
Summary
Identified TH transmembrane transporters (THTT) like monocarboxylate transporter 8 (Mct8) play a major role in uptake of TH across the BBB but as well in transport between cells like astrocytes and neurons within the brain. Already during the first trimester human brain expresses various TH transporters (see Table 1), Dio enzymes, TRisoforms, and isotypes in a development- and cell type-specific manner.
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