Fatty Acyl-CoAs Are Potent Inhibitors of the Nuclear Thyroid Hormone Receptor In Vitro

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We report that long-chain fatty acyl-CoAs are potent inhibitors of the thyroid hormone (T₃) receptor isolated from rat liver nuclei. Both saturated and unsaturated fatty acyl-CoAs were similarly potent. Fifty per cent inhibition of T³ binding by the receptor was observed at an oleoyl-CoA concentration as low as 1.3μM, and the affinity of oleoyl-CoA for the receptor (K₁) was estimated to be 0.45μM. Fatty acyl-CoAs also promoted dissociation of the hormone bound to the receptor. The action of fatty acyl-CoAs was competitive for the hormone binding site, resulting in a reduction in the receptor's affinity for T₃. These observations suggest that fatty acyl-CoAs modulate the binding of the thyroid hormone to its nuclear receptor, in vitro. Whether or not such events occur in vivo remains to be determined.