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 Sex-dependent expression and growth hormone regulation of class alpha and class mu glutathione S-transferase mRNAs in adult rat liver

1993 ◽  
Vol 294 (1) ◽  
pp. 159-165 ◽  
Author(s):  
P K Srivastava ◽  
D J Waxman
Keyword(s):  
Growth Hormone ◽  
Continuous Infusion ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Gh Treatment ◽  
Adult Rat ◽  
Hypophysectomized Rats

The sex-dependent expression and growth hormone (GH) regulation of rat liver glutathione S-transferase (GST) was examined using oligonucleotide probes that distinguish between closely related class Alpha (Ya1, Ya2, Yc) and class Mu (Yb1, Yb2, Yb3) GST mRNAs [Waxman, Sundseth, Srivastava and Lapenson (1992) Cancer Res. 52, 5797-5802]. Northern-blot analysis revealed that the steady-state levels of GST Ya1, Yb1 and Yb2 mRNAs are 2.5-3-fold higher in male as compared with female rat liver. In contrast, GST Yc and Ya2 mRNAs were expressed at a 2-3-fold higher level in female rat liver. Microsomal GST mRNA did not exhibit significant sex-dependent differences in rat liver. Treatment of male rats with GH by continuous infusion suppressed expression of the male-dominant GST Ya1, Yb1 and Yb2 mRNAs to levels at or below those found in female rat liver. This suppressive effect of GH was liver-specific, insofar as GH treatment did not alter kidney GST Ya1 mRNA levels. Hypophysectomy increased expression of the male-dominant GSTs, particularly in female rats (e.g. 8-fold elevation of GST Ya1 mRNA). GST Yc mRNA was increased approx. 2-fold in hypophysectomized males, indicating that this mRNA is subject to negative regulation by one or more pituitary-dependent factors. Continuous GH treatment of the hypophysectomized rats suppressed the expression of mRNA of GSTs Ya1, Yb1 and Yb2 when given as a continuous infusion, but not when given by an intermittent (twice daily) GH-injection schedule. Combination of continuous exposure to GH with thyroxine treatment resulted in a more complete suppression of GSTs Ya1, Yb1 and Yb2. In contrast, thyroxine increased the expression of GST Yc in hypophysectomized rats. These studies establish that several Alpha and Mu class GSTs are expressed in a sex-dependent fashion in adult rat liver, where they are regulated by multiple pituitary-dependent hormones through pretranslational mechanisms.

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.

OXYDATION DES ANABOLIKUMS 1-METHYL-ANDROST-1-EN-17β-OL-3-ON MIT WASSERSTOFFTRANSFER AUF ÖSTRON

1971 ◽  
Vol 67 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Martin Wenzel
Keyword(s):  
Rat Liver ◽  
Anabolic Steroid ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Liver Slices ◽  
Androgen Effects ◽  
Biochemical Difference

ABSTRACT With the aid of metenolon-17α-T a tritium-transfer to oestrone in rat liver slices was demonstrated. This tritium-transfer from metenolon17α-T to oestrone yielding tritium-labelled oestradiol had a higher efficiency in male than in female rat liver. Correspondingly in the presence of metenolon the relation of oestrone to oestradiol is changed more in male than in female rat liver. Looking for biochemical differences between the anabolic steroid metenolon and testosterone the oxydation at C17 was measured in different organs of the rat using 17α-T-labelled steroids. The highest oxydation rate was found for both steroids in the liver. In the sexual organs of male rats the oxydation rate of testosterone was 50–10 times higher than that of the anabolic steroid. This difference was less in sexual organs of female rats. This result of a greater biochemical difference between both steroids in males than in females leads to the question, whether the dissociation between the anabolic and the androgen effects is higher in males than in females.

Hypothalamo-pituitary regulation of the c-myc gene in rat liver

1990 ◽  
Vol 5 (3) ◽  
pp. 267-274 ◽  
Author(s):  
I. Porsch Hällstöm ◽  
J.-Å. Gustafsson ◽  
A. Blanck
Keyword(s):  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Continuous Administration ◽  
Gh Secretion ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Female Wistar Rats ◽  
Myc Gene

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.

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

EXPERIMENTAL EVALUATION OF DIURETICS IN THE RAT

1956 ◽  
Vol 34 (1) ◽  
pp. 903-911
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson
Keyword(s):  
Carbonic Anhydrase ◽  
Dose Range ◽  
Carbonic Anhydrase Inhibitor ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Female Rat ◽  
Inhibitor Type ◽  
Almost All

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.

AN ANALYSIS OF AN APPARENT SEX DIFFERENCE IN THE DESOXYRIBONUCLEIC ACID CONTENT OF RAT LIVER

1975 ◽  
Vol 80 (2) ◽  
pp. 319-328
Author(s):  
R. S. Leeuwin ◽  
B. J. Visser ◽  
C. v. d. Meer
Keyword(s):  
Sex Difference ◽  
Rat Liver ◽  
Dna Content ◽  
Testosterone Propionate ◽  
Liver Extract ◽  
Extraction Procedure ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Desoxyribonucleic Acid

ABSTRACT Using the extraction procedure of Schmidt & Thannhauser (1945) and the indole reaction for DNA according to Ceriotti (1952), the DNA content of female rat liver was about one and a half times that of male liver. Castration of male rats, with or without administration of testosterone propionate, had no effect on the liver DNA content. Spaying of female rats (5–6 weeks of age) caused a decrease of the liver DNA content. Substitution with oestradiol benzoate restored the amount of DNA. No significant sex difference was observed in the DNA content of either rat brain, kidney, spleen and thymus, or mouse liver. Dische's diphenylamine reaction showed no significant sex difference in the rat liver DNA content. It was concluded that rat liver may contain a substance which is controlled by oestrogens and which interferes with the indole reaction. The interfering factor is present in the protein fraction of the liver extract. The possible nature of this interfering substance is discussed.

scholarly journals Mode of GH administration and gene expression in the female rat brain

2017 ◽  
Vol 233 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Marion Walser ◽  
Linus Schiöler ◽  
Jan Oscarsson ◽  
Maria A I Åberg ◽  
Ruth Wickelgren ◽  
...  
Keyword(s):  
Mixed Model ◽  
Brain Regions ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Sexually Dimorphic ◽  
Female Rat ◽  
Expression Levels ◽  
Mixed Model Analysis ◽  
Significant Difference

The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron–haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5′-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.

TESTOSTERONE Δ4-REDUCTASE ACTIVITY IN RAT LIVER: HORMONAL CONTROL IN VIVO

1974 ◽  
Vol 63 (1) ◽  
pp. 181-189 ◽  
Author(s):  
D. C. PATTERSON ◽  
A. F. CLARK ◽  
C. E. BIRD
Keyword(s):  
Rat Liver ◽  
Reductase Activity ◽  
Enzyme Level ◽  
Hormonal Control ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Rate Limiting Step ◽  
Level Of Activity

SUMMARY The rate-limiting step in the metabolism of testosterone by the liver is reduction of the double bond in ring A. Using a spectrophotometric assay we have studied the effects of some hormonal manipulations on the levels (per mg protein) of testosterone Δ4-reductase activity in rat liver. While the levels of enzyme activity were higher for adult female rat liver than for adult male liver, there were no further changes in livers from female rats at day 15 of gestation. In male rats, castration increased, hypophysectomy decreased and adrenalectomy had no effect on the level of activity. Administration of oestradiol valerate increased the activity in intact and adrenalectomized animals and had no effect in the hypophysectomized or castrated groups. Administration of testosterone enanthate decreased the levels of activity in the castrated and adrenalectomized groups and had no effects in unoperated or hypophysectomized animals. When given together, the two hormones were antagonistic. Prolactin had no significant effects in either intact or hypophysectomized animals. Experiments with actinomycin D and cycloheximide indicated that the synthesis of new protein was involved in the effects of oestradiol in intact rats. All the changes reflected alterations in the microsomal enzyme level.

EXPERIMENTAL EVALUATION OF DIURETICS IN THE RAT

1956 ◽  
Vol 34 (5) ◽  
pp. 903-911 ◽  
Author(s):  
J. D. McColl ◽  
J. M. Parker ◽  
J. K.W. Ferguson
Keyword(s):  
Carbonic Anhydrase ◽  
Dose Range ◽  
Carbonic Anhydrase Inhibitor ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
High Dose ◽  
Female Rat ◽  
Inhibitor Type ◽  
Almost All

The diuretic response of the male and the female rat to aminophylline has been studied when these animals were pretreated with various concentrations of sodium chloride solution. A linear log dose – response curve was obtained over the dose range employed with male rats pretreated with 0.45% and 2% saline. Male rats exhibited a diuresis with 4% saline which was not increased by aminophylline. Female rats showed diuresis but the responses were more variable for almost all combinations of electrolyte load and xanthine dose. When they were pretreated with 0.45% and 2% saline, aminophylline caused some additional production of urine but this was much less regular than that observed with males. The variation in response to aminophylline after 4% saline was very marked but the trend suggested that the xanthine had a diuretic effect at the high dose. The diuretic responses to a xanthine, a mercurial, and a carbonic anhydrase inhibitor type of diuretic were compared in the male rat. Peak responses were smallest after the mercurial diuretic and greatest with the carbonic anhydrase inhibitor.

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