n-Butyrate enhances induction of thyroid hormone-responsive nuclear protein

Effects of n-butyrate on nuclear thyroid hormone receptors and on thyroid hormone-responsive nuclear protein were investigated by means of a perfusion system in rat liver. Treatment with 5 mM n-butyrate resulted in an increase (150%) in the maximal binding capacity of 3,5,3'-L-triiodothyronine (T3) nuclear receptors without altering the affinity of receptor for T3. However, further perfusion for 4 h decreased the number of the receptors to the control level. n-Butyrate increased the amount of acetylated histone H4. The ability of nuclear T3 receptors to bind to core histones was diminished by acetylation of the core histones. Thyroid hormone-responsive nuclear protein (n protein) was increased by T3. The induction of the n protein by T3 was augmented by n-butyrate. These results suggested that n-butyrate modulates thyroid hormone-responsive gene expression in rat liver via the increased number of nuclear receptors or changes in the chromatin constitution.