scholarly journals Sex-Related Liver Injury Due to Alcohol Involves Activation of Kupffer Cells by Endotoxin

2000 ◽  
Vol 14 (suppl d) ◽  
pp. 129D-135D ◽  
Author(s):  
Ronald G Thurman
Keyword(s):  
Liver Injury ◽  
Kupffer Cells ◽  
Coupling Constants ◽  
Female Rats ◽  
Male Rat ◽  
Gadolinium Chloride ◽  
Female Rat ◽  
Ethanol Treatment ◽  
Necrosis Factor Alpha ◽  
Rat Livers

Females have a greater susceptibility to ethanol-induced liver injury than males. Females who drink ethanol regularly and have been overweight for 10 years or more are at greater risk for both hepatitis and cirrhosis than males, and females develop ethanol-induced liver injury more rapidly and with less ethanol than males. Female rats on an enteral ethanol protocol exhibit injury more quickly than males and have widespread fatty changes over a larger portion of the liver lobule. Moreover, levels of plasma endotoxin, intracellular adhesion molecule-1, free radical adducts, infiltrating neutrophils and nuclear factor kappa B are doubled in female rat livers compared with male rat livers after enteral ethanol treatment. Additionally, estrogen treatment in vivo increases the sensitivity of hepatic macrophages or Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of ethanol-induced liver injury. Destroying Kupffer cells with gadolinium chloride or decreasing bacterial endotoxin by sterilizing the gut with antibiotics inhibits early inflammation due to ethanol. Similar results have been obtained with anti-tumour necrosis factor-alpha antibody. These data pointed to the hypothesis that ethanol-induced liver injury involves elevations in circulating endotoxin concentrations leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This theory has been tested using pimonidazole, a 2-nitroimidazole marker, to quantify hypoxia in downstream, pericentral regions of the hepatic lobule. After chronic enteral ethanol treatment, pimonidazole binding doubles. Enteral ethanol also increases free radicals detected with electron spin resonance. Radical adducts, with coupling constants such as alpha-hydroxyethyl radical, have been shown to arise from ethanol. Importantly, hypoxia and radical production detected in bile are also decreased by the destruction of Kupffer cells with gadolinium chloride. These data support the hypothesis that Kupffer cells contribute to the vital sex differences in liver injury caused by ethanol.

scholarly journals Novel Gender-Related Regulation of CYP2C12 Gene Expression in Rats

2005 ◽  
Vol 19 (5) ◽  
pp. 1181-1190 ◽  
Author(s):  
Megumi Endo ◽  
Yoshiki Takahashi ◽  
Yasumasa Sasaki ◽  
Tetsuya Saito ◽  
Tetsuya Kamataki
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Structure ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Hypersensitive Site ◽  
Responsive Element ◽  
Male Specific ◽  
Rat Livers

Abstract The expression of CYP2C12 by GH occurs in female but not in male rat livers. Direct injection of the CYP2C12 promoter-luciferase gene into male rat livers showed that the CYP2C12 promoter was active in both male and female rats. Thus, to further examine one or more factors that regulate the gender-related expression of CYP2C12, male rats were treated with trichostatin A, a specific inhibitor of histone deacetylase capable of condensing the chromatin structure. Interestingly, the expression of CYP2C12 by GH was seen even in the livers of male rats, indicating that histone deacetylase contributes to the suppression of CYP2C12 expression in male rats. Deoxyribonuclease I hypersensitive assay using nuclei from the livers of male or female rats revealed that the chromatin structure of the CYP2C12 gene was gender specific: a hypersensitive site at a position −4.2 kb containing GH-responsive element that bound to signal transducer and activator of transcription 5 (STAT5), termed as HS (hypersensitive site) 1, was specific for female rat livers, whereas a hypersensitive site at a position −3 kb, designated as HSm (male-specific hypersensitive site), was characteristic of male rat livers. A −3425/−3275 region within HSm functioned as a negative regulatory region, when the region was inserted in front of simian virus 40 promoter. Gel shift assay demonstrated that both CCAAT/enhancer-binding protein α and β bound to the −3425/−3275 region. Based on these results, we conclude that the gender-related expression of the CYP2C12 gene results from the inaccessibility of to STAT5 to the GH-responsive element by chromatin condensation seen in male rat livers, and from the presence of the male-specific HSm that acts as a silencer.

scholarly journals Sex differences in the hydroxylation of cholecalciferol and of 5 β-cholestane-3 α, 7 α, 12 α-triol in rat liver

1987 ◽  
Vol 247 (1) ◽  
pp. 73-78 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen
Keyword(s):  
Sex Hormones ◽  
Rat Liver ◽  
Female Rats ◽  
Regulatory Control ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Significant Difference ◽  
Alpha 7 ◽  
Rat Livers

The effect of sex hormones on hydroxylation of cholecalciferol (‘vitamin D3’) and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol has been investigated in female- and male-rat livers. The mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities were respectively 4.6- and 2.7-fold higher in female- than in male-rat livers. The microsomal 1 alpha-hydroxycholecalciferol 25-hydroxylase was 2.8-fold higher in male- than in female-rat liver. No significant difference was found in the microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Liver microsomes (microsomal fractions) from male, but not from female, rats also catalysed 1-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Injection of testosterone into female rats decreased the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities, but not to a statistically significant extent. Testosterone treatment had no effect on the microsomal hydroxylases in female-rat liver. Injection of oestradiol valerate to male rats resulted in increased activities of both mitochondrial hydroxylases to the same levels as those of control females, while the microsomal enzyme activities decreased. The present results indicate that sex hormones exert a regulatory control on the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities.

Sexual Behavior is Enhanced by Regular, Repeated Mating from Young Adulthood to Middle Age in Female Long-Evans Rats

2020 ◽  
Vol 13 (2) ◽  
pp. 169-177
Author(s):  
Fay A. Guarraci ◽  
Chantal M.F. Gonzalez ◽  
Devon Lucero ◽  
Lourdes K. Davis ◽  
Sarah H. Meerts
Keyword(s):  
Sexual Behavior ◽  
Mating Behavior ◽  
Preference Test ◽  
Sexual History ◽  
Female Rats ◽  
Male Rat ◽  
Female Rat ◽  
Repeated Mating ◽  
First Time ◽  
Mating Tests

Background: Aging is associated neuroendocrine changes in women. Animals can be used to model these changes, as well as changes in reproductive behavior. Objective: The current study was designed to characterize mating behavior across age and assess the effects of age and sexual history on mating behavior. Methods: Sexual motivation was assessed using the partner-preference test, in which a female rat is given the choice to interact with a same-sex conspecific or a sexually-vigorous male rat, with which she can mate. Results: Across repeated mating tests (2-12 months of age), female rats spent more time with the male, displayed more solicitation behaviors, were less likely to leave the male after mounts, but visited both stimulus animals less frequently. Comparing a separate group of age-matched, hormoneyoked female rats mated for the first time at 12 months of age to female rats mated for the first time at 2 months of age showed that the 12 month rats visited both stimulus animals less, were less likely to leave the male after mounts, took longer to return to the male after mounts, and displayed fewer solicitation behaviors than their younger counterparts. Relative to middle-aged female rats once they were sexually experienced, 12 month naïve rats spent less time with the male, were more likely to leave the male after mounts, and displayed fewer solicitation behaviors. Furthermore, 12 month naïve rats failed to discriminate between the stimulus animals, visiting both stimulus animals at the same rate unlike 2 month naïve or 12 month experienced rats. Conclusion: Taken together, these results suggest that aging affects some measures of sexual behavior, but most effects of age can be mitigated by regular, repeated mating.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

scholarly journals Mass spectrometric analysis of rat liver cytosolic glutathione S-transferases: modifications are limited to N-terminal processing

1995 ◽  
Vol 308 (1) ◽  
pp. 69-75 ◽  
Author(s):  
H I Yeh ◽  
C H Hsieh ◽  
L Y Wang ◽  
S P Tsai ◽  
H Y Hsu ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Female Rats ◽  
Spectrometric Analysis ◽  
Affinity Column ◽  
Female Rat ◽  
Significant Difference ◽  
Cytosolic Glutathione ◽  
Glutathione S Transferases ◽  
Molecular Masses ◽  
Rat Livers

Cytosolic glutathione S-transferases (GSTs) from rat livers were purified using an S-hexylglutathione affinity column. The GST subunits were resolved by reverse-phase HPLC and their molecular masses were determined by electrospray mass spectrometry. The major hepatic GSTs detected were subunits 1, 1′, 2, 3 and 4, with molecular mass of 25,520, 25,473, 25,188, 25,782 and 25,571 Da respectively. Subunits 6, 7 and 10 are minor components, with molecular mass of 25,551, 23,308 and 25,211 Da respectively. Alternatively, the hepatic GSTs were purified using a glutathione affinity column. Subunits 1, 1′, 2, 8 and 10 were eluted from this column with GSSG, the oxidized form of glutathione. Subunit 8 has a molecular mass of 25,553 Da. The remaining proteins on the glutathione affinity column were removed with glutathione and S-hexylglutathione. Subunits 2, 3, 4 and 6 could be detected in the eluate. We could not detect any significant difference in molecular mass between GSTs isolated from male and female rat livers. Cytosolic GSTs were isolated from livers of buthionine sulphoximine-treated female rats for MS analysis. The molecular masses obtained were identical to those determined for the controls.

Effects of acute administration of 2-hydroxylated metabolites of oestrogens on LH and prolactin secretion in male and female prepubertal rats

1984 ◽  
Vol 103 (3) ◽  
pp. 317-325
Author(s):  
A. K. Brar ◽  
G. Fink
Keyword(s):  
Plasma Concentration ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Uterine Weight ◽  
Immature Female ◽  
Male And Female ◽  
Immature Male ◽  
Lh Release

ABSTRACT The effects of catechol oestradiol and catechol oestrone on the release of LH and prolactin were investigated in immature male and female Wistar rats. In male rats both catechol oestradiol and catechol oestrone significantly increased the plasma concentration of LH, and catechol oestradiol but not catechol oestrone significantly increased the plasma concentration of prolactin and decreased the pituitary concentration of LH. The parent oestrogens, oestradiol-17β and oestrone, had no effect on plasma LH concentrations, but both increased significantly the plasma concentration of prolactin, and oestrone but not oestradiol-17β increased the pituitary concentration of LH. In immature female rats, catechol oestradiol inhibited the surge of LH and the increase in uterine weight induced by injecting pregnant mare serum gonadotrophin (PMSG). The injection of oestrone induced an increase in the plasma concentration of LH which was about nine times greater than that produced by oestradiol-17β. There were no significant differences in the effects of these steroids on plasma prolactin concentration. These results (i) confirm that in the immature male rat catechol oestrogens can stimulate LH release and show that catechol oestradiol can increase prolactin release, (ii) show that catechol oestradiol can inhibit the stimulatory effects of PMSG on LH release and uterine weight in the immature female rat, and (iii) demonstrate that oestrone can stimulate LH release in the immature female rat. J. Endocr. (1984) 103, 317-325

Subchronic Toxicity Studies Indicate that Tris(2-Chloroethyl)Phosphate Administration Results in Lesions in the Rat Hippocampus

1990 ◽  
Vol 6 (1) ◽  
pp. 1-15 ◽  
Author(s):  
H.B. Matthews ◽  
D. Dixon ◽  
D.W. Herr ◽  
H. Tilson
Keyword(s):  
Flame Retardants ◽  
Pyramidal Neurons ◽  
Rat Kidney ◽  
Female Rats ◽  
Male Rat ◽  
Repeat Dose ◽  
Female Rat ◽  
Synthetic Fibers ◽  
Ca1 Region ◽  
Liver And Kidney

Tris(2-chloroethyl)phosphate (TRCP), a flame-retardant plasticizer used in plastics, polymeric foams and synthetic fibers, was studied as part of the National Toxicology Program's class study of phosphate flame-retardants. TRCP was administered at 0, 22, 44, 88, 175 and 350 mg/kg to both sexes of rats and 0, 44, 88, 175, 350 and 700 mg/kg to both sexes of mice in both fourteen day repeat dose and sixteen week subchronic studies. Results of these studies showed that TRCP toxicity in the 14-day studies was limited to modest increases in male rat kidney and female rat liver weights. Little evidence of toxicity was observed in mice in the 14 day studies. Toxicity observed in mice in the sixteen week studies was limited to increased liver weights in both sexes and decreased kidney weights in males. Administration of TRCP to rats for sixteen weeks resulted in increased mortality of both males and females, increased liver and kidney weights and a lesion in the hippocampal region of the brain. The lesion observed in rat brain appeared as loss of the pyramidal neurons of the CA1 region of the hippocampus and was both more common and more severe in female rats. This lesion, which was not observed in mice, is unusual for any chemical and is unique for a trialkyl phosphate such as TRCP. It is speculated that this highly directed toxicity of TRCP might be used as a chemical probe to investigate the role of the hippocampus in behavior and other functions.

scholarly journals Monoclonal antibody LICR-LON-E36 recognizes gonadotrophs in female rat pituitaries.

1984 ◽  
Vol 32 (10) ◽  
pp. 1048-1054 ◽  
Author(s):  
P Monaghan ◽  
A P Sappino ◽  
J D Roberts ◽  
M A Knight ◽  
J Ellis ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicle Stimulating Hormone ◽  
Immunogold Labeling ◽  
Female Rats ◽  
Male Rat ◽  
Female Rat ◽  
Male And Female Rats ◽  
S 100 ◽  
Storage Granules ◽  
Electron Microscopical

The distribution of the antigen localized by monoclonal antibody LICR-LON-E36 has been studied by means of light and electron microscopical immunocytochemical procedures on resin-embedded pituitaries from male and female rats. Using both immunoperoxidase and immunogold labeling techniques, the localization of LICR-LON-E36 has been compared with that obtained with antibodies against the beta subunit of rat luteinizing hormone (beta LH) and human follicle stimulating hormone (beta FSH), porcine adrenocroticotropic hormone (ACTH) and rat S-100. LICR-LON-E36 is localized in a portion of beta LH-containing cells in female rat pituitaries and where present both antigens are localized within the same storage granules. LICR-LON-E36 is rarely detectable within beta LH-containing cells of male rat pituitaries that also stain positively with anti-beta FSH antibodies. ACTH and S-100 were localized within different cell populations.

scholarly journals Gender-dependent regulation of glutamate dehydrogenase expression in periportal and pericentral zones of rat liver lobules.

1996 ◽  
Vol 44 (10) ◽  
pp. 1153-1159 ◽  
Author(s):  
W J Geerts ◽  
M Verburg ◽  
A Jonker ◽  
A T Das ◽  
L Boon ◽  
...  
Keyword(s):  
Glutamate Dehydrogenase ◽  
Activity Patterns ◽  
Distribution Patterns ◽  
Female Rats ◽  
Male Rat ◽  
Male And Female Rats ◽  
Mrna Content ◽  
Males And Females ◽  
Rat Livers

We studied the level(s) at which glutamate dehydrogenase (GDH; EC 1.4.1.2) expression is regulated in the livers of fed male and female rats. The cellular content of GDH mRNA, protein, and enzyme activity was determined quantitatively using image analysis for measurement of the absorbance in consecutive serial sections that were processed for in situ hybridization, immunohistochemistry, and enzyme histochemistry. In both males and females, GDH protein and activity patterns were similar, with pericentral values being twice as high as periportal values. GDH mRNA distribution patterns in female liver lobules reflected those of GDH protein and activity, but GDH mRNA distribution patterns in male rat livers were found to be homogeneous owing to a more than twofold lower cellular mRNA content in pericentral zones than in female rats. We conclude that gender affects GDH expression selectively in pericentral zones at posttranscriptional and pretranslational levels.

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