Non-genomic actions of thyroid hormone in brain development
Department of Cellular and Molecular Physiology
Actins; Animals; Astrocytes; Brain; Cell Movement; Cerebellum; Humans; Models, Biological; Neurons; Protein Binding; Rats; Thyroid Hormones; Transcription, Genetic; Triiodothyronine
Life Sciences | Medicine and Health Sciences
Thyroid hormone (TH) is essential for neuronal migration and synaptogenesis in the developing brain. Assembly of neuronal circuits depends on guidance cues provided by the extracellular matrix. These cues are interpreted by the migrating neuron and its growing neurites through transmembrane signaling proteins anchored in place by the actin cytoskeleton. One of the best examples of a non-genomic action of thyroid hormone is its dynamic regulation of the number and quantity of actin fibers in astrocytes. Thyroxine (T4) and its transcriptionally inactive metabolite, 3',5',3-triiodothyronine (reverse T3) are responsible for modulating microfilament organization, while the transcriptional activator, 3',3,5-triiodothyronine (T3) is inert. The biological consequence of the loss of the actin filaments in astrocytes is the inability of the cell to anchor laminin, to its cell surface, and the loss of this key guidance molecule interrupts neurite pathfinding and neuronal migration. These data provide the essentials to construct a physiological pathway where TH-dependent regulation of the polymerization state of actin in the astrocyte and the developing neuron modulates the production and recognition of guidance cues--cues that if disrupted lead to abnormal neuronal migration and neuronal process formation--and lead to the morphological deficits observed in the cretinous brain.
DOI of Published Version
Steroids. 2008 Oct;73(9-10):1008-12. Epub 2007 Dec 27. Link to article on publisher's site
Leonard JL. (2008). Non-genomic actions of thyroid hormone in brain development. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.steroids.2007.12.016. Retrieved from https://escholarship.umassmed.edu/oapubs/1966