Relation of estrogen and its receptor to rat liver growth and regeneration.

A variety of hormones have been implicated in the process of liver regeneration. Despite the demonstration of specific estrogen receptors (ER) in mammalian liver and the identification of responses to estrogen which occur in liver, there has been little or no investigation of the relation of that hormone or its receptor to liver regeneration or liver growth. This report provides information which indicates: (a) the effect of 17 beta-estradiol on the mass of both intact and regenerating rat liver; (b) the percentage of hepatocytes in neonatal and adult normal intact livers which contain ER, i.e., the estrogen receptor index (ERI); (c) changes in ERI and in nuclear ER occurring in that cell population following partial hepatectomy (PH) and/or 17 beta-estradiol administration; and (d) the temporal relation of the changes in ER with those related to DNA synthesis and liver regeneration and to liver growth. Approximately 55 to 60% of parenchymal cells from intact livers in adult rats were found to contain ER which was entirely located in the cytoplasm. No nuclear ER was evident in such cells. By 1 hr, and subsequently following 17 beta-estradiol administration to such animals, there resulted a depletion in the number of ER-containing cells and the identification of nuclear ER. These changes were followed by the onset of increased DNA synthesis and an increase in liver weight (p less than 0.001). Subsequent to 70% PH, a similar series of events occurred in liver remnants. Not only was there a decrease in the ERI from 60% at the time of PH to 40% 3 hr later and 30% after 72 hr, there was a decrease in cytosol ER as well. Accompanying the decrease was an increase in the number of cells with nuclear ER. By 24 hr post-PH, 29% of the cells with ER displayed that receptor in their nuclei. At that time, DNA synthesis was at its peak, and liver regeneration was taking place. When 17 beta-estradiol was administered at the time of PH, there was a more rapid onset of translocation of ER to the nuclei of parenchymal cells. At PH, when 17 beta-estradiol was given, no cells displayed nuclear ER. One hr later, 18% of cells with ER had nuclear ER, in contrast to the finding that only 3% of cells had nuclear ER 1 hr post-PH when 17 beta-estradiol was not administered. Regeneration was greater (59 versus 73%; p = 0.003) when animals received 17 beta-estradiol prior to PH.(ABSTRACT TRUNCATED AT 400 WORDS)