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

Abstract

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.