Effect of thyroid deficiency on postnatal cell formation in the rat brain: a biochemical investigation.
In thyroid deficiency, interference with postnatal cell formation seems to be confined to those regions of the brain where postnatal neurogenesis is significant. In comparison with controls the increase in cell number in the cerebellum is retarded in the second week of life, but a normal number is reached by 35 days. In contrast the DNA content of the olfactory bulbs is apparently irreversibly depressed. Mitotic activity, in terms of incorporation of [2-14C]thymidine into DNA, is mainly affected in the cerebellum: in thyroid deficient rats, it is depressed below control levels at day 12, but it is about 4 times higher than in controls at day 21 when, under normal conditions, cell proliferation has virtually ceased. The time course (15-240 min) of [14C]thymidine metabolism at day 14 shows regional differences in control rats. The rate of conversion of [14C]thymidine to [14C]thymidine nucleotides, and of these in turn to [14C]DNA is slower in the forebrain - where cell proliferation occurs on a smaller scale - than in the cerebellum. Consequently, in the forebrain nearly linear DNA synthesis rate is maintained for a longer time than in the cerebellum (1 h vs. 0.5 h), and since less 14C is conserved in DNA a significant efflux of unconverted [14C]thymidine is evident during the experimental period. The effect of thyroid deficiency on [14C]thymidine metabolism in the brain is only slight, and is due to an abnormally large supply of [14C]thymidine consequent to depressed systemic utilization of this precursor.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division; D002531:Cerebellum / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D007037:Hypothyroidism / Q000378:metabolism / Q000473:pathology*; D009830:Olfactory Bulb / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D012313:RNA; D004247:DNA; D013936:Thymidine