Fatty acyl-CoAs are potent inhibitors of the nuclear thyroid hormone receptor in vitro.
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 microM, and the affinity of oleoyl-CoA for the receptor (Ki) was estimated to be 0.45 microM. 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.
Department of Biochemistry, Osaka City University Medical School.
Q L
QL
Li
N
N
Yamamoto
A
A
Inoue
S
S
Morisawa
D000214:Acyl Coenzyme A / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility
D000214:Acyl Coenzyme A; D011988:Receptors, Thyroid Hormone; C017585:oleoyl-coenzyme A