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The effect of estrogen and tamoxifen on hepatocyte proliferation in Vivo and in Vitro

Francavilla, A and Polimeno, L and Dileo, A and Barone, M and Ove, P and Coetzee, M and Eagon, P and Makowka, L and Ambrosino, G and Mazzaferro, V and Starzl, TE (1989) The effect of estrogen and tamoxifen on hepatocyte proliferation in Vivo and in Vitro. Hepatology, 9 (4). 614 - 620. ISSN 0270-9139

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Abstract

We have previously shown that changes in estrogen‐hepatocyte interaction occur during liver regeneration. Following 70% hepatectomy, estrogen levels in the blood were elevated, the number of estrogen receptors in the liver was increased and there was an active translocation of estrogen receptors from the cytosol to the nucleus. The injection of tamoxifen, an estrogen antagonist, inhibits hepatocyte proliferation following partial hepatectomy. The administration of 1 μg tamoxifen per gm body weight at zero time or 6 hr after the operation resulted in a significant inhibition both of DNA synthesis and of the number of cells in mitosis. Injections of tamoxifen 12 hr or later after the operation had no effect. Concomitant injections of equimolar amounts of estrogen abolished the inhibition by tamoxifen. The effects of estrogen and tamoxifen were also tested on hepatocytes in primary culture. Estrogens in the presence of 5% normal rat serum stimulated hepatocyte DNA synthesis as determined by [ 3 H]thymidine incorporation and the labeling index, whereas epidermal growth factor‐induced DNA synthesis in the absence of normal rat serum was strongly inhibited. Tamoxifen, in contrast, inhibited DNA synthesis of hepatocytes in the presence of 5% normal rat serum and reversed the stimulatory effect of estrogen in the same system. Attempts to elucidate the mechanism of tamoxifen inhibition in vitro indicated that one effect of tamoxifen is to prevent the amiloride‐sensitive Na + influx necessary to initiate hepatocyte proliferation. Copyright © 1989 American Association for the Study of Liver Diseases


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Francavilla, A
Polimeno, L
Dileo, A
Barone, M
Ove, P
Coetzee, M
Eagon, P
Makowka, L
Ambrosino, G
Mazzaferro, V
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1989
Date Type: Publication
Journal or Publication Title: Hepatology
Volume: 9
Number: 4
Page Range: 614 - 620
DOI or Unique Handle: 10.1002/hep.1840090417
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0270-9139
Other ID: uls-drl:31735062110451, Starzl CV No. 1004
Date Deposited: 08 Apr 2010 17:17
Last Modified: 16 Oct 2017 05:55
URI: http://d-scholarship.pitt.edu/id/eprint/4390

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