Effect of ovarian steroids on hepatic metabolism

Ms, Fahim; Dg, Hall; Jones, T.

doi:10.1016/0002-9378(71)90629-6

Cited by 10 publications

(1 citation statement)

References 13 publications

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“…In some cases, amounts of EtE2 corresponding to those given to humans for contraceptive purposes are sufficient to produce these effects. Our findings are in agreement with those of Fahim et al (1971) who demonstrated that male and female rats demethylated /?-chloro-N-methylaniline less efficiently after treatment with Eo and DES. That similar mechanisms may be operating in man is indicated by the studies by Crawford Sc Rudofsky (1966) who have demonstrated that women metabolize pethidine and promazine more slowly after taking oral contraceptives, and by O'Malley et al (1972) who have re¬ ported an increased plasma half-life time of antipyrine and phenylbutazone in women taking contraceptive steroids.…”

Section: Discussionsupporting

confidence: 96%

Dose-Dependent Effects of Ethinyloestradiol, Diethylstilboestrol and Oestradiol on the Metabolism of 4-Androstene-3, 17-Dione in Rat Liver Microsomes

Einarsson

Gustafsson

Sjövall

et al. 1975

Acta Endocrinologica

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The effects of administration of ethinyloestradiol (EtE2), 0.1, 0.5 or 1 \ g=m\ g per day, diethylstilboestrol, 5, 100 or 500 \ g = m\ g per day, and oestradiol, 1 or 100\g=m\gper day for 12 days on the hepatic microsomal metabolism of 4-[4-14C]androstene-3,17-dione were studied in castrated male and female rats.When rats were given EtE2 in daily doses of 0.1 and 0.5 \g=m\g the activities of the 3\g=a\-and 17\g=b\-hydroxysteroid oxidoreductases increased in both male and female rats. A similar tendency was noted for the 5\g=a\-reductasein female rats. On the other hand, the activities of the 3\g=b\-hydroxysteroid oxidoreductase and 7\g=a\-hydroxylaseenzyme systems were suppressed in both male and female rats already after administration of 0.1 \ g=m\ g of EtE2. Diethylstilboestrol, administered in doses of 100 and 500 \ g=m\ g, and oestradiol, given in a dose of 100 \g=m\g,suppressed the microsomal enzyme activities whereas the lower doses of 5 \g=m\g of diethylstilboestrol and 1 \ g=m\ g of oestradiol were without effects.The results indicate that oestrogenic compounds given in doses higher than the physiological one have a suppressing effect on microsomal steroid metabolizing enzyme activities. Ethinyloestradiol has a stimulating effect on certain microsomal enzyme activities and an inhibiting effect on others when administered in an amount of 0.5 \g=m\g\ m=. \ kg\m=-\1per day. The findings are discussed in relation to recent reports on impaired drug metabolism in women taking contraceptives.

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Section: Discussionsupporting

confidence: 96%

Dose-Dependent Effects of Ethinyloestradiol, Diethylstilboestrol and Oestradiol on the Metabolism of 4-Androstene-3, 17-Dione in Rat Liver Microsomes

Einarsson

Gustafsson

Sjövall

et al. 1975

Acta Endocrinologica

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Estrogen-Induced Cholestasis: Clues to Pathogenesis and Treatment

1983

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EditorialsEstrogen-Induced Cholestasis: Clues to Pathogenesis and Treatment Estrogen-related cholestasis has been of clinical interest for nearly three decades. The clinical spectrum of intrahepatic cholestasis of pregnancy and pruritus gravidarum was first characterized in 1955 (1-5). Although its pathogenesis remains unknown, epidemiologic and experimental data suggest an inheritable abnormality in hepatic reactivity to circulating estrogens. Oral contraceptives were introduced in 1960. It was soon observed that a small percentage of women using these drugs develop intrahepatic cholestasis (6-10, Sotaniemi, E. et al. Brit Med J 1964; 2:1264-1265, Correspondence) and approximately 50% of these individuals have intrahepatic cholestasis of pregnancy (11-13, Holzbach, R. T. and Sanders, H. H. Gastroenterology 1965;482322, Abstract). A "cholestatic" response to oral contraceptive steroids was noted in several hepatic disorders, including cirrhosis and the Dubin-Johnson syndrome (14-16). Data from rechallenge experiments suggests that the estrogenic component is the important agent, although progestins may augment the effect (17-21). The hepatic defect that enhances the effect of estrogens and the pathogenesis of cholestasis remain undefined. These clinical observations stimulated research into the concept that the liver is an important target organ for estrogenic effects and that estrogen-induced cholestasis is an excellent model for study of intrahepatic cholestasis.Recent basic science advances have advanced understanding of the molecular correlates of estrogen effects. Specific estrogen receptors have been demonstrated on plasma membranes (22-23) and in cytosol (24-26), microsomal components (27), and nuclei (25, 28) of hepatocytes in animals. The significance of these receptors is unclear; however, the data suggest that estrogen is transported across the plasma membrane and translocated to the nucleus. Within the nucleus, estrogens bind to DNA (29), stimulate RNA synthesis (30, 31), activate RNA methylating enzymes (32), and inhibit RNA deactivating enzymes (33).Hepatic effects of estrogens are dose-dependent. At the high levels achieved during pregnancy or with ad- ~ ~The authors were supported in part by RCDA (AM-00347) to Francis R. Simon and NIH Training Grant (T32 AM07038-07) to Allen J. Schreiber.

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Sex Hormones and the Liver

Thiel

Gavaler

1992

Modern Concepts in Gastroenterology Volume 3

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Effect of ovarian steroids on hepatic metabolism

Cited by 10 publications

References 13 publications

Dose-Dependent Effects of Ethinyloestradiol, Diethylstilboestrol and Oestradiol on the Metabolism of 4-Androstene-3, 17-Dione in Rat Liver Microsomes

Dose-Dependent Effects of Ethinyloestradiol, Diethylstilboestrol and Oestradiol on the Metabolism of 4-Androstene-3, 17-Dione in Rat Liver Microsomes

Estrogen-Induced Cholestasis: Clues to Pathogenesis and Treatment

Sex Hormones and the Liver

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