Estrogen Pharmacology

Tf, Gallagher; Mn, Mueller; Kappas, Attallah

doi:10.1097/00005792-196645060-00010

Cited by 76 publications

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“…It is possible that the infusion test will detect more abnormalities in women receiving oral contraceptives than the standard bromsulphthalein test. Progesterone does not impair bromsulphthalein excretion in laboratory animals (Gallagher et al, 1960) or in patients (Mueller and Kappas, 1964a). It is difficult to draw conclusions from the available evidence.…”

Section: Cholephil Excretionmentioning

confidence: 98%

“…The appearance of excessive amounts of conjugated bromsulphthalein in plasma during oestrogen treatment is consistent with an increase in the rate of reflux of the dye back into plasma from the liver as observed in pregnancy. Gallagher, Mueller, and Kappas (1960) examined the effects of a variety of natural and synthetic steroids on bromsulphthalein metabolism in the rat. Ten days' treatment with oestradiol and its metabolites, including oestrone and oestriol, produced impaired hepatic disposal of bromsulphthalein.…”

Section: Cholephil Excretionmentioning

confidence: 99%

“…In animals repeated doses of oestrogens (Gallagher et al, 1960) and progesterone (Hines, 1967) will increase liver weight. A single dose of oestrogen will not, however, increase liver weight (Thompson, Severson, and Reilly, 1966) although it will induce rapid uterine growth.…”

Section: Other Liver Enzymesmentioning

confidence: 99%

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Oral contraceptives and liver function

Hargreaves¹

1969

Journal of Clinical Pathology

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Section: Cholephil Excretionmentioning

confidence: 98%

Section: Cholephil Excretionmentioning

confidence: 99%

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Oral contraceptives and liver function

Hargreaves¹

1969

Journal of Clinical Pathology

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“…I t has been shown that high doses of exogenous estrogen may impair hepatic excretory function in human females and in the rat (1,2 ) . I t has been shown that high doses of exogenous estrogen may impair hepatic excretory function in human females and in the rat (1,2 ) .…”

mentioning

confidence: 99%

Effects of Ethinylestradiol-Induced Cholestasis on Bile Flow and Biliary Excretion of Estradiol and Estradiol Glucuronide by the Rat

Kreek

Peterson

Sleisenger

et al. 1969

Experimental Biology and Medicine

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The phenolic steroid hormones estrone and estradiol, are excreted in bile and undergo an enterohepatic circulation in the rat and in man. I t has been shown that high doses of exogenous estrogen may impair hepatic excretory function in human females and in the rat (1, 2 ) . There is also evidence that endogenous hormones may cause abnormalities of liver function or cholestasis during late pregnancy (3)(4)(5), and that in those individuals who have suffered from cholestatic jaundice of pregnancy or pruritus gravidarum, moderate or low dose of estrogen administered in the nonpregnant state will reproduce the symptoms and liver function test abnormalities that occurred during pregnancy (4, 5 ) . The present study was carried out to determine whether administered estrogen impairs bile flow and biliary excretion of labeled estrogen in the rat.Methods and Materials. Female Sprague-Dawley rats, weighing from 150 to 180 g were fed ethinylestradiol (0.5 mg in saline suspension, by oral tube) daily, for 9 days. Litter-mate control animals were similarly saline sham-fed. On the tenth experimental day common bile duct cannulation and femoral vein catheterization were performed with the rats under light ether anesthesia. Each animal was then confined to a modified plastic restraining cage. Constant intravenous hydration with 5% dextrose and saline solution administered by a Harvard infusion apparatus at a rate of 0.0764 ml/min, and constant room temperature conditions, 25-26', were maintained throughout the entire study. Public Health Service F2 A.M. -30,036.On the eleventh experimental day, 18-20 hr after surgery and 40-48 hr after the last dose of ethinylestradiol, a tracer dose of radioactive estrogen (estradiol or estradiol glucuronide) and bromsulfophthalein ( 10 mg) were administered intravenously via the femoral catheter, in 0.4 ml of 50% ethanolsaline solution, followed by a 1.0-ml saline flush. Bile was collected in 10-min fractions during the first hour, 15-min fractions during the second hour, 30-min fractions during the next 2 hr, and at 1-or 2-hr intervals up to a total of 9 hr. At the end of the collection periods, the animals were killed, the livers were examined grossly and under light microscopy with hematoxylin and eosin sections.Radioisotopes, estradiol-l7p-6, 7-3H, 5.6 Ci/mmole, istradiol-1 7P-4J4C, 8.18 mCi/ mmole and estradiol-6, 7-3H, 1 7/3-~-glucuronide, 1.0 Ci/mmole, were obtained from the New England Nuclear Corporation and were repurified by paper chromatography prior to use. The activity of the radioactive estrogen solutions to be administered was measured a t the time of each injection. Bile samples were measured for volume. Qualitative analysis for the appearance of bromsulfophthalein in the bile was made in all control and estrogentreated animals. Aliquots were taken for measurement of radioactivity. To each bile aliquot, 50 pl or less, was added 2 ml of ethanol and 10 ml of toluene-POPOP phosphor solution. Quench correction was carried out by the addition of an appropriate internal standard to ...

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“…These observations, along with reports of oestrogen receptors in the liver (Chamness, Costlow & McGuire, 1975) suggest that oestrogens exert considerable influence over the hepatic metabolism of lipids. Previous investigations (DeLorimier, Gordon, Lowe & Carbone, 1965;Gallagher, Mueller & Kappas, 1966) have suggested that the extent of the hepatic changes could be correlated with the molecular nature of the hormonal compound and might depend particularly on the 17\g=a\-alkyl-substitutedgroup in synthetic oestrogens. The influence of the ethynyl function in the 17\g=a\-position of oestradiol-17\g=b\ on the oestrogen-induced changes observed in hepatic lipases and serum levels of triglycerides has therefore been examined.…”

mentioning

confidence: 99%

Differential Effects of Oestradiol and Ethynyl Oestradiol on Lipid Metabolism in the Female Rat

Valette¹,

Carasco²,

Vérine³

et al. 1978

Journal of Endocrinology

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It has recently been shown that ethynyl oestradiol markedly decreases lipase activity in the liver (Valette, Verine, Salers & Boyer, 1977). These observations, along with reports of oestrogen receptors in the liver (Chamness, Costlow & McGuire, 1975) suggest that oestrogens exert considerable influence over the hepatic metabolism of lipids. Previous investigations (DeLorimier, Gordon, Lowe & Carbone, 1965;Gallagher, Mueller & Kappas, 1966) have suggested that the extent of the hepatic changes could be correlated with the molecular nature of the hormonal compound and might depend particularly on the 17\g=a\-alkyl-substitutedgroup in synthetic oestrogens. The influence of the ethynyl function in the 17\g=a\-position of oestradiol-17\g=b\ on the oestrogen-induced changes observed in hepatic lipases and serum levels of triglycerides has therefore been examined.Adult female Sprague-Dawley rats (220-240 g) were allowed free access to food and received oestradiol-17ß or ethynyl oestradiol (6 µg) by s.c. injection in 0-1 ml olive oil daily for 21 days. Controls received olive oil alone. The animals were killed and bled by decapita¬ tion. The liver was immediately excised, rinsed and homogenized at 4°C with three 1 min passes in a glass-Teflon homogenizer in a solution (10 ml/g) containing 0-25 M-sucrose, 2-5% glycerol and 10 mM-EDTA (pH 7-2). The homogenates were centrifuged sequentially at 600 # for 10 min, 10 000 # for 10 min, 25 000 g for 30 min and 100 000 # for 2 h to yield pellets numbered I, II, III and IV respectively. Pellets were resuspended in 50 mM-sodium phosphate buffer (pH 7-2) containing 5% glycerol and 0-1% Triton X-100. The suspensions were sonicated at 4°C (six times for 10 s, microtip, setting 1 with a Branson sonifier model 12) and then centrifuged at 100 000 g for 30 min. The supernatant fraction derived from pellet IV contained 60-80% of both the tri-and monoester lipase activities assayed at alkaline pH in the crude homogenate and served as the source of enzyme. Activity at alkaline pH corresponded to the hepatic lipases specifically sensitive to oestrogens (Valette et al. 1977). Triester lipase was assayed at 37°C in a final volume of 1 ml containing 0-1 ml Tris-HCl, 0-25% defatted albumin, 1 mM-tri-[3H]oleoylglycerol (106 counts/min) at a final pH of 8-0. The assay system for monoester lipase con¬ tained 0-1 mM-Tris-HCl, 0-5% defatted albumin and 1 mM-[3H]oleoylethanol (0-8 IO6 counts/min) in a final volume of 1 ml at 37°C (pH 8-5). In both cases, the release of [3H]oleic acid over the 15 min period of assay was monitored as described previously (Arnaud & Boyer, 1976). One unit of lipase activity corresponded to the release of 1 µ acid/min. Serum levels of triglycérides were determined according to the method of Van Handel «fe Zilversmit (1957).The data are shown in Table 1. Treatment with ethynyl oestradiol reduced the levels of hepatic tri-and monoester lipases by 59 and 22% respectively and these decreases in enzymic activity were associated with a 93% increase in the serum level of triglycér...

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Estrogen Pharmacology

Cited by 76 publications

References 0 publications

Oral contraceptives and liver function

Oral contraceptives and liver function

Effects of Ethinylestradiol-Induced Cholestasis on Bile Flow and Biliary Excretion of Estradiol and Estradiol Glucuronide by the Rat

Differential Effects of Oestradiol and Ethynyl Oestradiol on Lipid Metabolism in the Female Rat

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