Oligodendrocyte development and thyroid hormone

Thyroid hormone plays an important role in brain development and is essenti al to ensure a normal myelination, The effects of thyroid hormone are media ted by nuclear thyroid hormone receptors, which act as ligand-regulated tra nscription factors. There are several isoforms encoded by two genes, alpha and beta. Developmental studies have shown that alpha isoforms are widely e xpressed in the fetal brain, while beta isoforms expression is more restric ted with a dramatic increase that begins at birth in the rat. Remarkably, r eceptor number reaches maximal levels by postnatal day 10, when serum thyro id hormone levels also peak and myelination is the most prominent event in the developing rat brain. Likewise, oligodendrocyte precursor cells express alpha isoforms and expression of the beta isoforms is confined to the diff erentiated oligodendrocytes, suggesting that these isoforms might mediate d ifferent thyroid hormone effects in the oligodendrocyte lineage. Thyroid ho rmone acts at multiple steps in the development of oligodendrocytes: (a) Ea rly in development, it can function as an instructive signal for the genera tion of oligodendrocytes and enhance the proliferation of the committed pre precursor oligodendrocyte cells. (b) Thyroid hormone regulates the number o f oligodendrocyte generated by directly promoting their differentiation. Si nce oligodendrocytes are produced in vitro after the same period in culture regardless of whether thyroid hormone was added to the cultures, it has be en suggested that thyroid hormone is required for neither the timing nor th e generation of oligodendrocytes, but is necessary to achieve adequate olig odendrocyte numbers. (c) Finally, thyroid hormone increases morphological a nd functional maturation of postmitoitic oligodendrocytes by stimulation of the expression of various myelin genes. (C) 1999 John Wiley & Sons, Inc.