Effect of PTU treatment on histone acetylation pattern in the developing rat brain

The effect of hypothyroidism induced m female rats on histone acetylation p attern m the neonatal rat brain was studied. It is likely that thyroid horm one regulates the acetylation of histones and thereby influence their inter action with DNA and modulates transcription. Propylthiouracil (PTU), admini stered to induce hypothyroidism, resulted in a significant reduction m the thyroid and brain weight of neonatal rats. The circulating thyroxine levels were undetectable in both 14 and 21 day old pups. The hypothyroid conditio n was further confirmed by low levels of T4 (94.31 ng/g brain tissue vs 181 1.29 ng/g in controls and 144.67 ng/g vs 1087.72 ng/g in controls at 14 and 21 days, respectively) and T3 (42.19 ng/g brain tissue vs 879.97 ng/g in c ontrols and 60.62 ng/g vs 766.68 ng/g in controls at 14 and 21 days, respec tively) in the neonatal rat brain. Histone acetylation pattern was similar in treated and control groups m the 14 day old rats. PTU treatment, however , resulted in significant (p<0.01) reduction in acetylation in the H3 fract ion at 21 days whereas no such changes were recorded in other histone fract ions. Lower histone acetylation in the 21 day old pups suggest a reduction m the transcriptional activity due to fewer initiation sites for RNA polyme rase. It may be concluded that thyroid hormone may stimulate transcription of specific genes by increasing the acetylation of nucleosomal histones.