Techniques of quantitative histochemistry have been used for analysis of DNA and myelin components in developing somatosensory cortex of albino rats subjected at birth to (1) chronic hypothyroidism with initiation of hormonal replacement therapy at 10 postnatal days, and (2) chronic hyperthyroidism. Thyroxine administered in excess during early postnatal life results in a severe impairment of myelinogenesis in rat cerebral cortex by disrupting the normal sequence of glial cell mitosis, migration, and differentiation. Smaller doses of thyroid hormone, intended to produce a clinically euthyroid state in hypothyroid rats, is associated with a similar impairment of brain maturation despite rehabilitation of body growth. The failure of hormonal replacement therapy in the "cretin rat" may be ascribed, not merely to the delayed onset of treatment, but to a direct toxic effect of the hormone on the developing brain when delivered in amounts exceeding physiologic requirements.
Pelton EW, Bass NH. Adverse Effects of Excess Thyroid Hormone on the Maturation of Rat Cerebrum. Arch Neurol. 1973;29(3):145–150. doi:10.1001/archneur.1973.00490270027003
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