The role of thyroid hormone in fetal and neonatal brain development

Purpose of review: To understand how thyroid hormone regulates brain development it is important to identify thyroid hormone-responsive brain genes; determine how regulated expression of these genes affects brain cell development, physiology, and function; and determine how these physiologic changes affect brain function. The authors summarize recent studies contributing to the understanding of these processes and discuss important new studies that assess thyroid hormone metabolism in the developing brain. Recent findings: Specific thyroid hormone transporters are expressed in the developing brain. Recent data suggest that regulated expression, of these, transporters may control brain thyroid hormone influx and efflux. Additional data support a role for deiodinases in controlling local iodothyronine concentrations in the developing brain. A series of recent reports assesses the role of thyroid hormone in oligodendrocyte development and axonal myelination. These data provide a cellular and molecular explanation for the hypomyelinatton observed in neonates that have developed in a hypothyroid state. The cerebellar Purkinje cell is another well-described target of thyroid hormone in the developing brain. A recent study provides evidence that thyroid hormone acts directly on the Purkinje cell to regulate dendritic arborization. Finally, important new data provide insight regarding the functional effects of thyroid hormone deficiency on neuronal activity. Summary: Recent work has proyided exciting new insights regarding the mechanisms controllng thyroid hormone action in the developing brain. It seems likely that regulation of thyroid hormone metabolism and transport during brain development is a critically important mechanism of control. Additionally, important new findings have furthered our understanding of the structural and physiologic effects of thyroid hormone deficiency and excess on brain cell function.