In thyroid deficiency at birth, the endogenous pool sizes of cellular dTTP did not change much in the cerebellum, cerebrum and brain stem at the whole ages studied, but the specific radioactivities of dTTP, at 2 hours after the subcutaneous injection of [3H]-thymidine, apparently increased only in the cerebellum on the 14th and 21st days as compared with the normal controls. The highest rate of DNA synthesis in vivo, expressed in terms of the specific radioactivity ratio of DNA to dTTP, was observed at the four-day-old normal rat cerebellum, and in the thyroid deficiency it appeared to shift between seven and 14 days of age. On the other hand, no apparent effects of thyroid deprivation on the rates of both the cerebrum and brain stem were found. The results suggest that a temporal alteration of DNA synthesis as well as thymidine metabolism occurred by thyroid deficiency was confined to the cerebellum in the early postnatal development of rats. Indeed, cerebellar thymidine kinase activity, related to DNA synthesis, also displayed a concomitant delay in thyroid deficiency to the characteristic age-dependence of DNA synthesis. No significant difference between normal and thyroidectomized rats was revealed in this respect on both the cerebrum and brain stem throughout the experimental periods.

Animals↗

PubMed1977

Effects of neonatal thyroidectomy on thymidine metabolism and deoxyribonucleic acid synthesis in the developing rat cerebellum.

Thyroid deficiency at birth caused a temporal decrease of the DNA content in rat cerebellum during the periods from 7 to 21 days of life as compared with the normal. At 2 h following the subcutaneous injection of [3H]-thymidine, the specific radioactivity of cellular dTTP in thyroid deficient rats was apparently increased on the 14th and 21st days, although the endogenous pool sizes of dTTP did not significantly differ between the normal and thyroidectomized rats throughout the entire ages studied. The ratio of incorporation of thymidine into cerebellar DNA was initially determined by the specific radioactivity and then expressed as the ratio of [3H]-DNA to [3H]-dTTP, the relative specific radioactivity of DNA. The age peak of incorporation occurred at 7 days in the normal; on the other hand, the specific activity of DNA in thyroid deficiency attained a maximum at 14 days and the relative specific activity appeared to be prolonged up to 14 days. The corresponding changes were observed in the formation of dTTP, suggesting that a transient retardation of cerebellar DNA synthesis taking place by neonatal thyroidectomy may be in part attributable to the variance of phosphorylation of thymidine. Indeed, thymidine kinase activity that regulated salvage pathway for DNA synthesis displayed a parallel variation in thyroid deficiency to characteristic age dependence of DNA synthesis.

Animals↗

PubMed1977