Development-related changes of triiodothyronine binding to brain cytosol receptors

Abstract

SEVERAL lines of evidence have established that thyroid hormones have a major role in the functional differentiation of the mammalian central nervous system^1–4. Clinical or experimental hypothyroidism in early life results in behavioural disturbances and mental dysfunction which are apparently the outward manifestation of well-defined biochemical and structural lesions observed in the cerebellum and cerebral cortex of experimental animals. Significantly, the defects arising from the hypothyroid state are amenable to hormone therapy only during an early critical age period. Furthermore, unlike the liver and most other tissues, the mature brain is not responsive to the manipulation of the thyroid hormone state at least in terms of certain biochemical parameters. The brain is thus uniquely dependent on thyroid hormones for the full expression of functional development during a limited age period which is analogous to the situation in amphibian metamorphosis⁵. I reasoned that the acquisition and disappearance of brain sensitivity to thyroid hormones may be related to their binding properties with cellular receptors. I show here that the affinity of rat brain (cerebellum) cytosol for triiodothyronine (T₃) is high during an early age period when cytodifferentiation is most intense and declines dramatically with age with no apparent change in the number of binding sites. In sharp contrast, the liver shows a marked increase in the number of binding sites with age with little change in affinity.