TY - JOUR
T1 - Effects of ethinylestradiol and norethisterone on liver microsomal metabolism of steroids in male and female rats
AU - Einarsson, Kurt
AU - Ericsson, Jan L.E.
AU - Gustafsson, Jan Åke
AU - Sjövall, Jan
AU - Zietz, Eberhard
N1 - Funding Information:
This investigation was supported by grants from the Swedish Medical Research Council (13X-219) and from W.H.O. One of us (E.Z.) thanks the Deutsche Forschungsgemeinschaftf or financial support.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1974/12/17
Y1 - 1974/12/17
N2 - The effects of administration of ethinylestradiol (17α-ethinyl-1,3,5(10)-estratriene-3, 17β-diol), 5 or 500 mg · kg-1 per day, and norethisterone (17β-hydroxy-17α-ethinyl-4-estren-3-one), 0.5 or 50 mg · kg-1 per day, for two weeks on the hepatic microsomal metabolism of 5α-[4-14C]androstane-3α,17β-diol, 4-[4-14C] and rostene-3,17-dione, 4-[4-14C] pregnene-3,20-dione and 7α-hydroxy-4-[6β-3H] cholesten-3-one and on the fine structure of parenchymal cells were studied in male and female rats. The low dose of ethinylestradiol suppressed most hydroxylase levels and increased 5α-reductase levels in male rats in a manner consistent with a feminizing effect of the drug. Female rats reacted much less to the low dose of ethinylestradiol although 5α-reductase levels were slightly but significantly reduced. The high dose of ethinylestradiol suppressed most enzyme activities both in male and female rats. The low dose of norethisterone stimulated some hydroxylase and oxidoreductase activities in the metabolism of 4-androstene-3,17-dione, 4-pregnene3, 20-dione and 7α-hydroxy-4-cholesten-3-one. In contrast, the high dose reduced these activities in both male and female rats. No alterations in the fine structure of hepatic parenchymal cells were observed following the administration of ethinylestradiol or norethisterone. It is concluded that ethinylestradiol affects hepatic steroid hydroxylation and reduction mainly in male rats and by virtue of its estrogenic, demasculinizing effect, and that it causes a general suppression of the steroid metabolizing enzymes in rats of both sexes when given in the large doses, 500 mg · kg-1, commonly used in previous studies. Norethisterone, like progesterone, increases the activities of a few hydroxylases but generally suppresses.
AB - The effects of administration of ethinylestradiol (17α-ethinyl-1,3,5(10)-estratriene-3, 17β-diol), 5 or 500 mg · kg-1 per day, and norethisterone (17β-hydroxy-17α-ethinyl-4-estren-3-one), 0.5 or 50 mg · kg-1 per day, for two weeks on the hepatic microsomal metabolism of 5α-[4-14C]androstane-3α,17β-diol, 4-[4-14C] and rostene-3,17-dione, 4-[4-14C] pregnene-3,20-dione and 7α-hydroxy-4-[6β-3H] cholesten-3-one and on the fine structure of parenchymal cells were studied in male and female rats. The low dose of ethinylestradiol suppressed most hydroxylase levels and increased 5α-reductase levels in male rats in a manner consistent with a feminizing effect of the drug. Female rats reacted much less to the low dose of ethinylestradiol although 5α-reductase levels were slightly but significantly reduced. The high dose of ethinylestradiol suppressed most enzyme activities both in male and female rats. The low dose of norethisterone stimulated some hydroxylase and oxidoreductase activities in the metabolism of 4-androstene-3,17-dione, 4-pregnene3, 20-dione and 7α-hydroxy-4-cholesten-3-one. In contrast, the high dose reduced these activities in both male and female rats. No alterations in the fine structure of hepatic parenchymal cells were observed following the administration of ethinylestradiol or norethisterone. It is concluded that ethinylestradiol affects hepatic steroid hydroxylation and reduction mainly in male rats and by virtue of its estrogenic, demasculinizing effect, and that it causes a general suppression of the steroid metabolizing enzymes in rats of both sexes when given in the large doses, 500 mg · kg-1, commonly used in previous studies. Norethisterone, like progesterone, increases the activities of a few hydroxylases but generally suppresses.
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U2 - 10.1016/0005-2760(74)90142-8
DO - 10.1016/0005-2760(74)90142-8
M3 - Article
AN - SCOPUS:25344459899
SN - 0005-2760
VL - 369
SP - 278
EP - 293
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 3
ER -