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Effect of spironolactone and potassium canrenoate on cytosolic and nuclear androgen and estrogen receptors of rat liver

Francavilla, A and Di Leo, A and Eagon, PK and Polimeno, L and Guglielmi, F and Fanizza, G and Barone, M and Starzl, TE (1987) Effect of spironolactone and potassium canrenoate on cytosolic and nuclear androgen and estrogen receptors of rat liver. Gastroenterology, 93 (4). 681 - 686. ISSN 0016-5085

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Abstract

Spironolactone and potassium canrenoate are diuretics that are used widely for management of cirrhotic ascites. The administra tion of spironolactone frequently leads to feminization, which has been noted less frequently with the use of potassium canrenoate, a salt of the active metabolite of spironolactone. The use of these two drugs has been associated with decreases in serum testosterone levels and spironolactone with a reduction in androgen receptor (AR) activity. This decrease in AR has been cited as the cause of the antiandrogen effect of these drugs. We therefore assessed the effect of both drugs on levels of androgen and estrogen receptors (ER) in the liver, a tissue that is responsive to sex steroids. Three groups of male rats (n = 12 rats each) were studied. Group 1 (control) received vehicle only; group 2 received spironolactone (5 mg/day); group 3 received potassium canrenoate (5 mg/day). After 21 days of treatment, the animals of all groups were killed and liver tissue was assayed for nuclear and cytosolic AR and ER, and for male specific estrogen binder (MEB), an androgen-responsive protein. Both drugs drastically decreased the nuclear AR content, as compared with the control group, but only spironolactone decreased cytosolic AR. When the total hepatic content of AR is considered, a highly significant decrease is observed only in rats treated with spironolactone. This reduction in hepatic AR content suggested loss of androgen responsiveness of liver. We confirmed this by assessing levels of MEB, and found that livers from group 2 animals had no detectable MEB activity, whereas livers from both group 1 and 3 had normal MEB activity. No changes were observed in nuclear ER and cytosolic ER of group 3 as compared with group 1. Nuclear estrogen receptor decreased and cytosolic ER increased in group 2, but with no change in total ER content. These results indicate that (a) only spironolactone appears to act as an antiandrogen in liver, resulting in a decrease in both AR and male specific estrogen binder content, and (b) neither drug results in elevated hepatic ER content, although spironolactone-treated animals show an altered subcellular localization. © 1987.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Francavilla, A
Di Leo, A
Eagon, PK
Polimeno, L
Guglielmi, F
Fanizza, G
Barone, M
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1987
Date Type: Publication
Journal or Publication Title: Gastroenterology
Volume: 93
Number: 4
Page Range: 681 - 686
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0016-5085
Other ID: uls-drl:31735062119304, Starzl CV No. 736
Date Deposited: 08 Apr 2010 17:12
Last Modified: 28 Oct 2017 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/4122

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