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.
Li
Q L
QL
Department of Biochemistry, Osaka City University Medical School.
Yamamoto
N
N
Inoue
A
A
Morisawa
S
S
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