A lack of thyroid hormone (T4) during early postnatal life produces a delay or arrest of cell proliferation, migration, and differentiation in the brain, and reduced myelination. On the other hand, growth hormone (GH) deficiency also impairs cell migration and oligodendroglial differentiation, with subsequent failure of myelination. Both the above findings appear to act via a similar mechanism, a thyroid-pituitary linkage. Neonatal thyroid dysfunction produces a striking alteration of the pituitary gland, characterized mainly by degradation of eosinophil cells, which appear to synthesize or store GH. For this reason, the effect of GH on brain growth in neonatally thyroidectomized animals has been intensively studied, but the results are still controversial and inconclusive.Pituitary-deficient Snell dwarf mice (dw) exhibit severe growth retardation shortly after birth, owing to defective anterior pituitary glands which secrete very low amounts of GH, prolactin, thyroid-stimulating hormone (TSH) and possibly corticotrophin. The Snell dwarf mouse, therefore, appears to be ideally suited for studying the effects of growth stimulating factors, not only somatic but also on cerebral development.Differences in the brain weights of the dwarf and control mice first became apparent on the 10th day of age, and from this time on no further increase in the weight of the dwarf mouse brain was recorded. Increase in 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity (myelinmarker enzyme) was found to be suppressed in the cerebrum and brain stem throughout the devel-opmental stage, but not in the other parts of the brain. Differences in DNA content per cerebrum from the dwarf and control mice first became apparent on the 10th day of age. Henceforth, the dwarf mice showed no further increase, although the normal controls continued to increase. [3H] -Thymidine incorporation into DNA fraction in vivo on the 7th day of age, when glial cell proliferation in the cerebrum is most active, was suppressed to about half of the control level in all parts of the dwarf brain. These findings indicate that the poor myelination found in the dwarf cerebrum is a hypomyelination due to reduced oligodendroglial proliferation. Furthermore, we also demonstrated the faulty development of cortical neurons in the dwarf cerebrum.On the next step, we investigated the effect of GH, TSH, and T4 on myelinogenesis by monitoring the activity of the CNPase. The results obtained in this study suggest that acceleration of retarded myelinogenesis, possibly through the enhancement of glial cell division, depends essentially upon the GH level plus the synergistic effects of T4. In addition, we also demonstrated that exogenous OH and T4 will enhance neuronal growth in the Snell dwarf cerebrum, and retore neuronal arborization to normal.To determine whether the two hormones, GH and T4, canact independently, we used a prom-ising animal model, the inherited primary hypothyroid mouse (hyt), which has a hypoplastic thyroid gland because of an autosomal recessive mutation. CNPase activity in the cerebrum of this mutant is also reduced in comparison with the normal control. However, no differences were observed with regard to DNA and RNA contents and RNA/DNA ratio. These results indicate that hypomyelination in the hypothyroid mouse is restricted to the cerebrum, and is not related to arrest glial proliferation. In addition, no morphological abnormalities of cortical neurons were observed in the cerebrum, although hypomyelination was present.To determine whether GH has an independent action on cerebral development, we examined the central nervous system of the Little mouse (lit), a promising model of isolated growth hormone deficiency Type I. Our findings are that; the weight of two parts of the lit brain, the cerebrum and