Effect of thyroid hormone T3 and T4 on the central nervous system is associated with diabetes mellitus

Thyroid hormones are critically involved in the development of the central nervous system (CNS). Fetal and/or neonatal hypothyroidism causes myelination defects, and neuronal migration and differentiation, which cause mental retardation, which can be profound, and in certain cases irreversible neurological alterations. It is accepted that most of the actions of the thyroid hormones are due to the interaction of the active thyroid hormone, triiodothyronine (T3), with nuclear receptors. Thyroid hormone regulates the expression of a series of genes that encode proteins with very diverse physiological functions: myelin proteins, proteins involved in cell adhesion and migration, signaling proteins, cytoskeleton components, mitochondrial proteins, transcription factors, etc. T3 originates partially in the thyroid gland, but for the most part is generated locally in target tissues from thyroxine (T4 ). The concentration of T3in the CNS is tightly regulated by type II and III 2 deiodinases. Type II deiodinase, which is expressed in tanycytes and astrocytes, produces up to 80% of the T3present in the CNS. Type III deiodinase, present in neurons, degrades T4 and T3to inactive metabolites. In the human fetus, the T3 receptor is present at least from the 10th week of gestation, indicating that thyroid hormone may have actions in the human fetal brain. Of course, in human fetal tissues, T4 can be detected in most of them, and T3 in the brain, which could be derived mostly from T4.