The effects of diethylstilbestrol, tamoxifen, and toremifene on estrogen-inducible hepatic proteins and estrogen receptor proteins in female rats.
Alterations of estrogen-inducible hepatic proteins and estrogen receptor proteins were studied in female rats after daily oral administration of vehicle control (0.5% carboxymethylcellulose), the nonsteroidal antiestrogens tamoxifen (TAM; 3, 11, or 45 mg/kg body weight), toremifene (TOR; 3, 12, or 48 mg/kg body weight), or the potent synthetic estrogen diethylstilbestrol (DES; 10 mg/kg body weight) for 1 and 3 months. Serum corticosterone levels were significantly reduced by TAM 11, TOR 12, and DES at 1 month and by TOR 48 and DES at 3 months. Serum ceruloplasmin levels were unchanged at 1 month except for a significant reduction with TOR 48 and a significant increase in the DES-treated group. After 3 months, all doses of TAM and TOR had significant reductions whereas DES had elevations even greater than those at 1 month. The activity of the enzyme alanine aminotransferase in the liver was increased by TAM, TOR, and DES at 1 and 3 months of treatment. Both TAM and TOR caused a slight reduction in cytosolic estrogen receptor protein after 1 month and significant reductions at 3 months. The nuclear estrogen receptor (nER) protein levels were significantly increased at 1 and 3 months for TAM and TOR; whereas DES treatment resulted in nER levels no different than controls. In summary, chronic (up to 3 months) administration of TAM and TOR results in qualitatively and quantitatively similar hormone-related effects on the female rat liver. Thus, other mechanisms must be investigated to ascertain the hepatoproliferative differences seen with TAM administration but not with TOR.
Kendall
M E
ME
American Health Foundation, Division of Nutrition and Endocrinology, Valhalla, New York 10595.
Rose
D P
DP
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D003345:Corticosterone / Q000097:blood; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017312:Toremifene
D002352:Carrier Proteins; D004967:Estrogens; D011506:Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004054:Diethylstilbestrol; D017312:Toremifene; D000410:Alanine Transaminase; D003345:Corticosterone