Effect of chromatin associated factors on the activity of thyroid hormone receptors in rat liver and brain

Receptors for thyroid hormones were extracted by 0.4 M KCl from the nuclei of rat liver and brain, and their binding properties compared to the properties of these receptors in unextracted nuclear suspensions. The inhibititory effect of a non-iodinated thyroid hormone analogue, 3,5,dimethyl-3′-isopropyl-l-thyronine (DIMIT) on ¹²⁵I]-T₃ binding was observed in the nuclear suspension of brain, but absent when the solubilized receptors of the same organ were tested. The initial properties of the receptor could be restored in a system containing the receptor and the extracted chromatin. Moreover, when the liver solubilized receptor was supplemented with the brain chromatin extract, the hepatic receptor acquired the binding ability of the brain receptors. The data suggest that chromatin associated components may confer organ specificity in thyroid hormone effects, and play a role in the selectivity of the recognition of thyroid hormone analogues by the receptor.