A study of the effect of hormone and growth factor on liver regeneration

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In an attempt to elucidate the mechanisms of liver regeneration, the changes of protooncogene expression (c-myc, fos, Ha-ras, erbA), estrogen receptor (ER) and vitamin D receptor (VDR) were investigated in rat regenerating liver at different times after partial hepatectomy(PH).Levels of c-fos mRNA elevated quickly to 2.5-fold within 45 min after PH and also decreased rapidly by 1h, c-myc mRNA reached maximal level of 3 fold at 3h and fell to basal level within 8h. Levels of c-Ha-ras elevated to 2-fold at 12h, but c-erbA mRNA did not demonstrate any significant increase during liver regeneration. Alternatively, c-myc mRNA were also demonstrated in hepatocyte cytoplasm by in situ hybridization method at 3h and myc protein product in hepatocyte nuclei at 6th immunohistochemically.Recently, a close relationship between oncogene products and hormone receptor or growth factor or its receptor were indicated, therefore we investigated ER and VD-R which have some association with erbA and myc genes respectively. ER rapidly declined to 1/2-fold of basal level at 3h, despite no change in erbA. VD-R which was not detected in preoperative liver, became detectable and reached a peak at 6h after PH.Hence, the parallelism in change of c-myc and VD-R expression suggested that there is a close relationship between c-myc and VD-R expression in hepatocyte. To investigate whether estrogens are able to promote liver regeneration, we treated rat with estradiol before PH. However, we were unable to obtain a result which indicated that estrogen raises significantly liver volume in 7 days, although ER stayed at a low level for long duration compared to non treated rats.Unfortunately the evaluation of the effect of active vitamin D and growth factor, especially epidermal growth factor on liver regeneration remains to be done.