Effect of hydrocortisone on the synthesis of DNA and histones and the acetylation of histones in regenerating liver

Pretreatment of rats with pharmacological doses of hydrocortisone for 1 to 5 days prior to partial hepatectomy strongly inhibited the rise in liver DNA synthesis which normally reaches a peak 24 hr after partial hepatectomy. However, 2 to 4 days after partial hepatectomy there was a partial recovery of DNA synthesis in the treated animals. The degree of inhibition of histone synthesis was considerably less than that of DNA, and only the synthesis of the slightly lysine-rich histones was closely coupled in time and relative magnitude with DNA synthesis. Synthesis of the lysine-rich and arginine-rich histone fractions was much less inhibited, and the rates of synthesis of these fractions increased prior to the delayed rise in DNA synthesis. The early increase in acetylation of the arginine-rich histone fractions after partial hepatectomy was not significantly affected by pretreatment with hydrocortisone. On the other hand, pretreatment with hydrocortisone strongly inhibited the late (24 hr) rise in acetylation of histone fraction f2a2. Hydrocortisone did not inhibit DNA synthesis in a transplanted hepatoma, but it did inhibit DNA synthesis in the livers of tumor-bearing animals.