Abstract
To determine whether GH has an independent action on cerebral development, we examined the central nervous system of thelittle mouse (lit), a promissing model of isolated growth hormone deficiency. Our findings are (A); the weights of two parts of thelit brain were significantly less than those of the normal controls, 81.5% less for the cerebrum, and 81.6% for the cerebellum, (B): the total DNA content was reduced to approximately 80% in the cerebrum and 84% in the cerebellum compared to those of the normal controls, (C); the total RNA content was also reduced in the cerebrum and cerebellum, proportional to the reduction in DNA, (D); CNPase activity was reduced selectively in the cerebrum of thelit mouse (74.4% of the normal control), and (E); thelit mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. These results indicate that GH has independent actions on cerebral development, especially on glial cell proliferation as a precondition of myelin formation.
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Noguchi, T., Sugisaki, T., andTsukada, Y. 1982. Postnatal action of growth and thyroid hormones on the retarded cerebral myelinogenesis of Snell dwarf mice (dw). J. Neurochem. 38:257–263.
Noguchi, T., Sugisaki, T., Takamatsu, K., andTsukada, Y. 1982. Factors contributing to the poor myelination in the brain of the Snell dwarf mouse. J. Neurochem. 39:1693–1699.
Noguchi, T., Sugisaki, T., Watanabe, M., Kohsaka, S., andTsukada, Y. 1982. Effects of bovine growth hormone on the retarded cerebral development induced by neonatal hydrocortisone intoxication. J. Neurochem. 38:246–256.
Smith, P. E., andMacDowell, E. C. 1931. The differential effect of hereditary mouse dwarfism on the anterior pituitary hormone. Anat. Rec. 50:85–93.
Bartke, A. 1964. Histology of the anterior hypophysis, thyroid and gonads of two types of dwarf mice. Anat. Rec. 149:225–236.
Beamer, W. G., Eicher, E. M., Maltais, L. J., andSouthard, J. L. 1981. Inherited primary hypothyroidism in mice. Science 212:61–63.
Beamer, W. G., andCresswell, L. A. 1982. Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice. Anat. Rec. 202:387–393.
Noguchi, T., andSugisaki, T. 1984. Hypomyelination in the cerebrum of the congenitally hypothyroid mouse (hyt). J. Neurochem. 42:891–893.
Noguchi, T., Sugisaki, T., Satoh, I., andKudo, M. 1985. Partial restauration of cerebral myelination of the congenitally hypothyroid mouse by parenteral or breast milk administration of T4. J. Neurochem. in press.
Sarlieve, L. L., Bouchon, R., Koel, C., andNeskovic, N. M. 1983. Cerebroside and sulfatide biosynthesis in the brain of the Snell dwarf mouse: effects of thyroxine and growth hormone in the early postnatal period. J. Neurochem. 40:1058–1062.
Solomon, J., andGreep, R. O. 1950. The effect of alteration on thyroid function in the pituitary growth hormone content and acidophil cytology. Endocrinology 65:158–164.
Contopoulos, A. M., Simpson, M. E., andKoneff, A. A. 1958. Pituitary function in the thyroidectomized rat. Endocrinology 63:642–653.
Herlant, M. 1964. The cells of the adenohypophysis and their functional significance. Int. Rev. Cytol. 17:299–382.
Schooley, R. A., Friedkin, S., andEvans, E. S. 1966. Reexamination of the discrepancy between acidophil numbers and growth hormone concentration in the anterior pituitary following thyroidectomy. Endocrinology 79:1053–1057.
Daughaday, W. H., Peake, G. T., Birge, C. A., andMariz, I. K. 1968. The influence of endocrine factors in the concentration of growth hormone in rat pituitary.in Pecile, A. andMüller, E. E. eds.), Proc. Int. Symp. Growth Hormone, Milan, Italy, Sep. 11–13, 1967, Pages 238–252. Excerpta Medica, Amsterdam.
Eicher, E. M., andBeamer, W. G. 1976. Inherited ateliotic dwarfism in mice; characteristics of mutation, Little, on chromosome 6. J. Heredity 67:87–91.
Cheng, T. C., Beamer, W. G., Phillips, J. A. III, Bartke, A., Mallonee, R. L., andDowling, C. 1983. Etiology of growth hormone deficiency in Little, Ames, and Snell dwarf mice. Endocrinology 113:1669–1678.
Kurihara, T., andTsukada, Y. 1967. The regional and subcellular distribution of 2′,3′-cyclic nucleotide 3′-phosphohydrolase in the central nervous system. J. Neurochem. 14:1167–1174.
Tsukada, Y., Nagai, K., andSuda, H. 1980. A rapid micro method for 2′,3′-cyclic nucleotide 3′-phosphohydrolase assay using micro high performance liquid chromatography. J. Neurochem. 34:1019–1022.
Schmidt, G., andThannhauser, S. J. 1945. A method for the determination of deoxyribonucleic acid, ribonucleic acid, and phosphoproteins in animal tissue. J. Biol. Chem. 161:83–89.
Burton, K. 1956. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem. J. 62:315–323.
Mejbaum, W. 1939. Über die bestimmung kleiner Pentosemengen, insbensondere in Derivation der Adenylsäure. Z. Physiol. Chem. 258:117–120.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein in measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Noguchi, T., Sekiguchi, M., Sugisaki, T., Tsukada, Y., andShimai, K. 1983 Faulty development of cortical neurons in the Snell dwarf cerebrum. Devl. Brain Res. 10:125–138.
Noguchi, T., Sugisaki, T., andTsukada, Y. 1984. Stimulation of Snell dwarf mouse neuronal growth by GH and T4. Neurochem. Path. 2:123–138.
Sugisaki, T., Noguchi, T., andTsukada, Y. 1985. Cerebral myelinogenesis in the Snell dwarf mouse: stimulatory effects of GH and T4 restricted to the first 20 days of postnatal life. Neurochem. Res. 10:767–778.
Laron, Z., andGalatzer, A. 1980. Aspects of brain development in children and adolescents with pituitary growth hormone deficiency, Pages 293–302.in DeWied, D., andVan Keep, P. A. (eds.), Hormones and the brain, MTP Press, Lancaster, England.
Howard, E. 1965. Effects of cortisone and food restriction on growth and on RNA/DNA and cholesterol content of brain and liver in infant mice. J. Neurochem. 12:181–191.
Schapiro, S. 1971. Influence of hormonal and environmental stimulation on brain development, in Influence of Hormones on the Nervous System. Proc. Int. Soc. Psychoneuroendocrinol., Brooklyn, 1970, Pages 63–73.
Westermark, B., Westeson, A., andUthene, K. 1975. Initiation of DNA synthesis of stationary human glia-like cells by polypeptide fraction from human plasma containing somatomedin activity. Exp. Cell Res. 96:58–62.
Heldin, C.-H., Wateson, A., Frykland, L., andWestermark, B. 1981. Somatomedin B: Mitogenic activity derived from contaminant epidermal growth factors. Science 213:1122–1123.
Noguchi, T., andSugisaki, T. 1985. Abnormal neuronal growth in the Little (lit) cerebrum. Exp. Neurol. 89: in press.
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Dedicated to Professor Yasuzo Tsukada.
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Noguchi, T., Sugiasaki, T. & Tsukada, Y. Microcephalic cerebrum with hypomyelination in the growth hormone-deficient mouse (lit). Neurochem Res 10, 1097–1106 (1985). https://doi.org/10.1007/BF00965884
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DOI: https://doi.org/10.1007/BF00965884