There is considerable evidence that the biological actions of thyroid hormones within the cell are mediated by binding to specific iodothyronine receptors found in close association with nuclear chromatin (1). There is an excellent correlation between the binding of T3 analogues to nuclear receptors and their thyromimetic potency. A second line of evidence is the correlation between the sensitivity of tissues to thyroid hormone action and the concentration of nuclear receptor sites in that tissue. Tissues such as the anterior pituitary and liver which are highly responsive to thyroid hormones have large numbers of nuclear receptors for T3, but tissues such as the testis and spleen, which are unresponsive to thyroid hormones, have little or no demonstrable nuclear binding. There is a clear relationship between nuclear occupation and nuclear response; when nuclear sites are fully saturated the measured biological response is maximal. The rapidity with which certain mRNA sequences change in response to T3 occupation of the nuclear sites further supports the concept of a causal relationship between the two. The receptor has been characterised as a non-histone protein of molecular weight 50,000 and a sedimentation coefficient of 3.5S. The receptors are of high affinity (Ka 5 × 1010 1/mol) and are an integral component of a larger unit, the receptor-containing chromatin complex.
KeywordsThyroid Hormone Thyroid Hormone Receptor Chloramphenicol Acetyl Transferase Thyroid Hormone Action Hypothyroid Animal
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