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EXPERIMENTAL HYPOTHYROIDISM: RELATIONSHIP BETWEEN CEREBELLAR CELL DIVISION AND ENZYMES INVOLVING NUCLEIC ACID METABOLISM DURING DEVELOPMENT

Perinatal hypothyroidism in the rat results in a delay in the developmental spectrum of cerebellar cell replication with a shift to a later age in the developmental spectrum of activity of thymidine kinase (TK), a salvage pathway enzyme active in replicative DNA synthesis. In the present experiments hypothyroidism was induced by administration of propylthiouracil (PTU) to the mother from the 18th day of gestation. We measured cerebellar activities of uridine kinase (UK), aspartate transcarbamylase (ATC), and thymidylate synthetase (TS). These enzymes are associated with the salvage of uridine, de novo synthesis of uridylate, and conversion of uridylate to thymidylate respectively, and their peak activities normally occur near the time of most rapid cerebellar DNA synthesis. Activities of ATC at age 3 days and TS at age 5 days were significantly decreased to 91.3% and 94% of control respectively, while activities were significantly elevated to 116% and 142% of control by day 15. UK activity was unaffected by hypothyroidism after 5 days of age. The shift to a later age in the developmental spectrum of ATC and TS supports the possibility that the de novo and interconversion pathways relate closely to replicative DNA synthesis, whereas the salvage pathway for uridine may relate more closely in brain to the synthesis of RNA and the sustaining of non-dividing cells.