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Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Kahn, D and Gavaler, JS and Lai, H and Makowka, L and Eagon, PK and Francavilla, A and Starzl, TE and Van Thiel, DH (1990) Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy. Digestive Diseases and Sciences, 35 (1). 6 - 11. ISSN 0163-2116

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Abstract

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P < 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P < 0.01) and thymidine kinase activity (P < 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P < 0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kahn, D
Gavaler, JS
Lai, H
Makowka, L
Eagon, PK
Francavilla, A
Starzl, TEtes11@pitt.eduTES11
Van Thiel, DH
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1990
Date Type: Publication
Journal or Publication Title: Digestive Diseases and Sciences
Volume: 35
Number: 1
Page Range: 6 - 11
DOI or Unique Handle: 10.1007/bf01537215
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0163-2116
Other ID: uls-drl:31735062116680, Starzl CV No. 1114
PubMed ID: 2295296
Date Deposited: 08 Apr 2010 17:19
Last Modified: 13 Oct 2017 21:59
URI: http://d-scholarship.pitt.edu/id/eprint/4500

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