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Care should be exercised in relating observations in the rat
to the clinical problems of human beings. It is important to bear
in mind that many of the thyroid hormone-dependent changes in
brain development occurring after birth in the rat take place
during the last trimester of gestation in human pregnancy. Thus,
fetal hypothyroidism in the later stages of pregnancy in human
beings may have more profound effects than those observed in the
comparable period in the rat.
The observation that small quantities of T3 and T4 are present in fetal rats together with thyroid hormone receptors has been widely interpreted to suggest that the hormone and its receptors play a critical role in the very early development of the central nervous system. If valid, such a role for thyroid hormone would be a reasonable explanation for the so-called neurological cretinism characterized by spastic paralysis. The data from the studies reported here, however, would suggest that the simple identification of thyroid hormone receptors and thyroid hormone in brain does not necessarily connote active function. Our findings suggest that developmentally regulated factors bound to TREs are capable of blocking any premature effects of T3 and TRs, and that the simple presence of T3 and TRs at a given stage of brain development cannot by themselves establish a functional role of thyroid hormone at that level. |
