Effect of thyroid hormone on the biochemical maturation of rat brain: Postnatal cell formation

(1) Treatment with thyroid hormone (triiodothyronine, T 3) in early life reduced the rate of growth in the rat: at 50 days of age the weights of the body and the brain were 20–30% less than those of controls. During the period of relatively rapid growth of the brain its size was less reduced than was that of the body. However the size of the brain corresponding to body weights exceeding 40–50 g was less than in controls. (2) The growth of the brain is related not only to an increase in the size of cells existing at birth, but also to an increase in their number amounting in the cerebrum to 80% of the number at birth and in the cerebellum to a rise by a factor of 35. The rate in the deposition of DNA is most rapid during the period from 5 to 14 days when it is about 3 times faster in the cerebellum than in the cerebrum; the rapid rate also continues later in life in the cerebellum than in the cerebrum. These observations indicate that in respect to the final assembly of cells the cerebellum develops later than the cerebrum. (3) The reduced brain size in rats treated with T 3 is caused by a permanent reduction in the final cell number. Evidence is summarized which indicates that treatment with T 3 affects cell formation rather than cell destruction, resulting in a 30–40% reduction in the number of cells formed after birth. The effect develops at a considerable time after the treatment has been started, and becomes significant about a week later in the cerebellum (at the end of the second week of life) than in the cerebrum. These observations suggest that the sensitivity of the tissue to thyroid hormone depends on the developmental state of the cells. The findings are consistent with the view that treatment with T 3 results in a premature termination of cell proliferation that is related to an acceleration of either the differentiation of the cells or their migration from germinating sites. Postnatal cell formation in the rat brain involves neurones as well as glial cells. Hence the reduction in postnatal cell formation may be involved in the impairment of the adaptive behaviour of rats treated with thyroid hormone. (4) By contrast to the marked effect on cell number treatment with T 3 did not affect the growth of the cells in the brain. There was no alteration in the maturational changes related to cell size: the packing density of the cells, the concentration of cell constituents and the cellular contents of RNA and protein respectively were similar to thos