摘要:

Male, but not female, rat liver cytosol contains an estrogen‐binding protein with unique properties: rapid binding of estradiol, high binding capacity, moderate affinity for estradiol, and specificity for steroidal estrogens and weak androgens, but not for nonsteroidal estrogens or other steroids. The estradiol‐binding activity of this protein is reduced in cytosol from livers of alcohol‐fed rats as compared to that from their isoca‐lorically fed controls. The properties of this male‐specific hepatic estrogen‐binding protein suggest a role for this protein in the regulation of estrogen levels in the male animal. Moreover, the reduction in activity of this unique protein in the liver of alcohol‐fed animals may explain, at least in part, the feminization commonly seen in chronic

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04885.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Although epidemiological data suggest that the development of cirrhosis in alcohol abusers is related to the duration and amount of ethanol intake, the fact that only a small percentage of alcohol abusers develop cirrhosis remains unexplained and suggests a possible predisposing genetic factor. Several previous studies have reported an association between various human leucocyte antigens (HLA) and alcoholic cirrhosis. In this study HLA antigen frequencies were determined in Anglo‐ and Spanish‐American cirrhotic and noncirrhotic alcoholics and in a control group of nonalcoholic patients without liver disease. No statistically significant differences in HLA frequencies among the groups were found. Our comparisons of HLA frequencies between cirrhotic and noncirrhotic alcoholic patients do not support the hypothesis that individual susceptibility to the development of alcoholic cirrhosis is genetically determi

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04886.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The effects of chronic ethanol consumption on thyroid hormone levels and the rates of whole animal and perfused liver oxygen consumption were determined to test the hypothesis that alcoholic liver damage is a result of thyroid mediated liver hypermetabolism (L. Videla, J. Bernstein, and Y. Israel:Biochem.J, 134: 507–514, 1973). Whole animal minimal oxygen consumption, a sensitive indicator of the effects of thyroid hormone (W. D. Denckla: J.Clin.Invest, 53:572–581, 1974) was unchanged in rats maintained 3 wk on a liquid diet containing 34% of the calories as ethanol (2.49 ± 0.06 ml of O2/min/1O0 g of fat‐free body weight) when compared to animals fed an equicaloric sucrose containing liquid diet (2.61 ± 0.20 ml of 02/min/100 g of fat‐free body weight) or Purina chow (2.50 ± 0.12 ml of O2/min/100 g of fat‐free body weight). Ethanol treatment lowered serum thyroxine (5.09 ± 0.20 pg/100 ml) compared to sucrose‐fed control rats (7.66 ± 0.40 pg/100 ml), while serum triiodothyronine was unaffected (59.3 ± 4.0 compared to 66.9 ± 3.1 ng/100 ml for controls). Measurement of O2consumption in the isolated perfused rat liver showed no significant difference after chronic treatment with the ethanol diet compared to either the sucrose or chow control diets. Infusion of 10‐7M norepinephrine into the perfusion medium resulted in an approximately 22% increase in O2consumption in ethanol‐fed animal and sucrose controls, while a 31 % increase was observed for sucrose‐treated animals given 10 μg of T3/kg of body weight/day for 3 wk. These data indicate that T3potentiates the ability of norepinephrine to increase O2consumption. The data presented give no support to the concept that chronic ethanol ingestion results in hyperthyroidism or liver hypermetabolism and, consequently, the rationale for treatment of alcoholic hepatitis with the antithyroid drug, propylthiouracil, is incorrect (H. Orrego, H. Ka‐lant, Y. Israel, et al.:Gastroe

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04887.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Male mice selected for genetic differences in ethanol‐induced sleep time, thereby designated long sleep (LS) and short sleep (SS), were treated with the Lieber‐DeCarli liquid diet for 25 days. This chronic ethanol treatment produced an increase in liver/body weight and kidney/body weight in SS mice only. In addition, chronic ethanol treatment produced significant increases in both LS and SS treated mice in in vivo ethanol elimination, hepatic cytochromes P‐450 and Bs, NADPH cytochrome c reductase and hepatic and renal 7‐ethoxycoumarin O‐de‐ethylase activity. Geno‐typic differences were observed in the magnitude of response of microsomal ethanol oxidation per mg of microsomal protein (SS>LS). Further, control LS and SS mice possessed substantially different activity of renal 7‐ethoxycoumarin O‐de‐ethylase. Both lines exhibited similar induced renal 7‐ethoxycoumarin O‐de‐ethylase activity after chronic ethanol ingestion. Ethanol binding spectra produced when ethanol was added to hepatic microsomes were examined using double reciprocal plots. Chronic ethanol ingestion produced genotypically related (LS>SS) increases in the absorbance change maximum per mg of microsomal protein. No significant changes in the spectral dissociation constant or absorbance change maximum per nM cytochrome P‐450 were observed

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04888.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Intragastric intubation of 4 or 8 g/kg of body weight of ethanol per day for 12 consecutive days disrupted the normal estrous cycle in female rats as monitored by vaginal epithelial cell changes. Plasma luteinizing hormone levels were unchanged suggesting that blood ethanol in the 50–100 mg/100 ml range acted as a direct gonadal toxin and not at the hypothalamic‐pitui‐tary gland

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04889.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Medical histories of the 15,924 male twin pairs in the National Academy of Sciences‐National Research Council Twin Registry were examined to determine, within pairs, concordances for alcoholism and its medical end points. Prevalences per 1,000 among individual twin subjects were 29.6 for alcoholism, 4.1 for alcoholic psychosis, 14.2 for liver cirrhosis, and 2.1 for pancreatitis. Prevalences were similar for monozygotic (MZ) and dizygotic (DZ) twins. Prevalences in percent among co‐twins of diagnosed subjects, that is case‐wise twin concordance rates, were, respectively, by diagnosis: alcoholism: 26.3 (MZ), 11.9 (DZ); alcoholic psychosis: 21.1 (MZ), 6.0 (DZ); and liver cirrhosis: 14.6 (MZ), 5.4 (DZ). No twin pairs concordant for pancreatitis were found.The greater concordance for alcoholic psychosis and for liver cirrhosis among MZ than DZ twins could not be explained by the difference in alcoholism concordance between them. The difference in concordance between MZ and DZ twins persisted when, in addition, it was assumed that only half of the actually occurring cases of alcoholism and of each of the end points have been ascertained. These results provide evidence in favor of genetic predisposition to organ‐specific complications of alcoholism and should serve to stimulate searches for the underlying biochemical mec

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04890.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

An extensive alcoholism history questionnaire was administered individually to 102 alcoholics. The results were analyzed by averaging the mean age of first occurrence of each symptom for the whole group, and separately by focusing on the order of appearance within each individual subject. The results of these two approaches are presented and compared.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04891.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Hepatic blood flow measured by indocyanine green clearance was studied in rats after an acute intoxicating dose of ethanol (2 g/kg) or after chronic ethanol administration by feeding with alcohol liquid diets. Acute intoxication to normal animals did not modify hepatic blood flow. In chronically alcohol‐fed rats, hepatic blood flow was significantly decreased when measured after 15 hr of abstinence. If ethanol was not withdrawn and an acute dose of ethanol was given before the indocyanine green clearance, a decreased hepatic blood flow was not observed. It is suggested that the reduction of hepatic blood flow in recently abstinent chronically alcohol‐treated animals is related to the withdrawal syndr

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04892.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Sterol metabolism studies usinag a combination of iso‐topic and chromatographic procedures were carried out in two strains of rats fed 5% ethanol (36% of calories) in the diet.Feeding ethanol to the Fisher rat over 17 days produced no significant changes in body weight. Cholesterol levels in various tissues were elevated in the ethanol‐fed group: plasma cholesterol, +61%; liver cholesterol, +47%; and bile cholesterol, +57%. The alcohol‐fed Fisher rat showed several changes in sterol metabolism over controls: fecal acidic steroid output, + 13%; fecal neutral sterol output, +51%; endogenous neutral sterol output, +107%; cholesterol turnover, + 54%; and cholesterol balance, +18%.Ethanol feeding to the Spraque Dawley rat showed similar differences between ethanol‐fed vs. control rats. Cholesterol levels were significantly elevated in plasma (+35%) and in the liver (+81%). Sterol metabolism data showed the following differences (alcohol vs. control): fecal acidic steroid output, +9%; fecal neutral sterol output, +17%; endogenous neutral sterol output, +72%; cholesterol turnover, +33%; and cholesterol balance, +13%.The Fisher rat maintained almost constant weight throughout the experimental period and is a preferable strain for sterol balance studies using liquid diets. A major finding of these experiments was the increased concentration of cholesterol in liver, plasma, and bile in both strains of rats. The sterol balance measurements indicated that this tissue accumulation of cholesterol was due to enhanced cholesterol synthesis as well as inhibition of bile acid sy

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04893.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Ethanol is a known inducer of microsomal enzymes as well as a testicular toxin. In order to evaluate the effect of chronic ethanol ingestion upon the microsomal enzymes required for testosterone synthesis, we examined the activity of four testicular enzymes (3β‐hydrex‐ysteroid dehydrogenase/isomerase, 17α‐hydroxylase, 17,20‐lyase, and 17β‐hydroxysteroid dehydrogenase) in 14 pairs of adult chronic alcohol‐fed rats and their age‐matched isocaloric controls. Ethanol feeding enhanced the activity of 17,20‐lyase when expressed as either activity/mg of protein (p<0.05) or activity/g of testis (p<0.025). Similarly, the activity of 17α‐hydrox‐ylase was increased in testes of the alcohol‐fed animals (p<0.025) compared to controls. In contrast, chronic ethanol feeding reduced total activity of 3β‐hydroxy‐steroid dehydrogenase/isomerase in alcohol‐fed animals (p<0.05) compared to controls. No effect of ethanol feeding was seen on activity of 17β‐hydroxy‐steroid dehydrogenase. Based upon these studies we conclude that chronic ethanol ingestion (1) increases testicular 17α‐hydroxylase and 17,20‐tyase and (2) reduces 3β‐hydroxysteroid dehydrogenase/isomerase in rat testicular microsomes. Therefore, we would propose that the major effect of chronic ethanol ingestion upon the enzymes required for testosteronogenesis is the reduction of 3β‐hydroxysteroid dehydrogenase/ isomerase activity, the rate limiting

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1981.tb04894.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY