Human chorionic gonadotropin and inhibin induce histone acetylation in human breast epithelial cells

We have previously demonstrated that human chorionic gonadotropin or hCG-induces differentiation of the mammary gland. The effect of hCG was accompanied by the synthesis of inhibin, a heterodimeric protein that is structurally related to the transforming growth factor-beta (TGF-beta) family and activation of c-myc, c-jun, testosterone repressed prostate message 2 (TRPM2) and interleukin-l-beta-converting enzyme (ICE) transcripts. In the present work we aim to demonstrate that hCG and inhibin may control the transcription of these genes by acetylation of histones in the breast epithelial cells. For this purpose we have utilized MCF-10F cells in culture to detect the levels of acetylated histone H3 and H4 after treatment with different concentrations of hCG as well as inhibin beta-subunit at various time points. In the Western blot analysis, both acetylated histone H3 and H4 were significantly increased by hCG treatment over 12 h in MCF-10F cells at all the doses tested. Inhibin induced the accumulation of acetylated histone H3 after 4-h-treatment at the concentration of 1 ng/ml and at all the time points with higher concentration (10-1000 ng/ml). Slight induction of acetylated histone H4 was detected only in the cells treated with inhibin at 100 ng/ml for 12 and 24 h. This study is the first one to demonstrate that these hormones increase the acetylation of histones.