Thyroid Hormone and the Neuroglia: Both Source and Target

Figure 4

Proposed model of neuroglia-neuron interaction of thyroid hormone signaling in the brain. D2 activates the prohormone T4 in glial cells (astrocytes and tanycytes); the generated T3 exits the glial compartment and enters adjacent neurons, where it establishes a transcriptional footprint via liganding TR. Only the two best-characterized thyroid hormone transporters, OATP1C1 and MCT8, are indicated, but data are also accumulating on the role of LAT1 and LAT2 in the thyroid hormone transport both in neurons and astrocytes (discussed in Section 1). In the glial compartment LPS activates D2 transcription while sonic hedgehog (Shh) promotes D2 inactivation via WSB1—mediated ubiquitination; both hypoxia and Shh activate D3 gene transcription in neurons. Figure modified from Freitas et al. American Society for Clinical Investigation [23].