FATTY ACYL-COAS ARE POTENT INHIBITORS OF THE NUCLEAR THYROID-HORMONE RECEPTOR INVITRO

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 1.3 μM, and the affinity of oleoyl-CoA for the receptor (K1) was estimated to be 0.45 μM, 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. © 1990 COPYRIGHT, 1990 BY THE JOURNAL OF BIOCHEMISTRY.