Y. Muller et J. Clos, IS THYROID-HORMONE A CLOCK-GOVERNING HORM ONE DURING THE DEVELOPMENT OF THE CENTRAL-NERVOUS-SYSTEM, MS. Medecine sciences, 13(1), 1997, pp. 116-122
The development of the nervous system follows two models: the instruct
ive or clonal model (expression of genetic information) and the select
ive model (regulation during a critical period of gene expression by h
ormones or growth factors (auto-selective), or by epigenetic factors s
uch as nutrition, environment, etc.). The two processes that character
ize development, proliferation and cell differentiation, are regulated
independently. The alpha receptor of T3 (alpha T3R) is constitutively
expressed in neuronal and glial cell lines. Without T3, or in the pre
sence of T3 but in the absence of transcription factors likely to form
heterodimers with this receptor (e.g. the alpha RXR receptor of 9-cis
-retinoic acid), growth factors (PDGF, NGF, NT-3, IGF) do regulate the
mitotic activity of neuroblasts and glioblasts. The presence of T3 (r
esulting from the onset of thyroid activity and from the increased tis
sue capacity for deiodation of T4) and (or) the appearance of transcri
ption factors likely to interact with RT3 alpha to form a functional h
ormone-receptor unit, leads to blocking of the cell cycle; it then ini
tiates cell differentiation, probably by inhibiting the AP1 complex, w
hich induces mitotic activity and represses differentiation in many ce
ll types. The action of T3 is followed by spatial coordination of the
establishment of the synaptic network, in parallel with temporal regul
ation of cell differentiation (cytoskeletal development and neuritogen
esis) and of the survival (apotosis) of its constitutive elements. Con
comitantly, T3 controls the appearance of, or the overexpression of, i
ts beta receptor. Thyroid hormone plays an essential role in the tempo
ral regulation of proliferation, differentiation and cell survival, di
rectly and (or) in a permissive way via growth factors and neurotrophi
ns, the synthesis of which is hormone-dependent. This makes it one of
the determinant neurotropic factors involved in the structural reorgan
ization and functional adaptations that characterize the plasticity of
the developing nervous tissue.