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.

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.

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.

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.

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.

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.

Differential regulation of prolactin receptor mRNA expression in rat liver and kidney by testosterone and oestradiol

1994 ◽  
Vol 143 (2) ◽  
pp. 383-392 ◽  
Author(s):  
K Sakaguchi ◽  
T Ohkubo ◽  
T Sugiyama ◽  
M Tanaka ◽  
H Ushiro ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Rat Liver ◽  
Short Form ◽  
Differential Regulation ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Female Rat ◽  
Long Form ◽  
Liver And Kidney

Abstract Prolactin (PRL) exerts a wide variety of physiological effects on mammalian tissues through its receptor (PRL-R) on the target cells. PRL-R in rat tissue consists of two isoforms, the long and the short form, and the regulatory mechanisms of their mRNA expression in tissues are complex and diverse. The present study reports the differential regulation of PRL-R mRNA expression in rat liver and kidney by testosterone and oestradiol. Using Northern blot analysis, short form PRL-R mRNA was clearly detected in female rat liver and male rat kidney, and long form PRL-R mRNA was faintly observed only in female rat liver. However, the reverse transcription-polymerase chain reaction method enabled efficient analysis of mRNA levels in short and long forms of PRL-R in the liver and kidney of both male and female rats. The mRNA levels for the long and short forms of PRL-R were depressed in the liver of male rats but not in that from female rats during sexual maturation. Castration of male rats resulted in the induction of the mRNAs for these two forms of PRL-R in the liver. Testosterone, but not oestradiol, completely blocked the induction by castration of liver PRL-R gene expression. In kidney, in contrast, mRNA levels for both forms of PRL-R were depressed in female rats but not in male rats after sexual maturation. Administration of oestradiol, but not of testosterone, caused marked repression of short form PRL-R mRNA, particularly in the kidney of male rats. The levels of long form PRL-R mRNA in the kidney was less affected by the administration of oestradiol. These results have suggested that the expression of PRL-R mRNAs in rat liver and kidney is differentially regulated by testosterone and oestrogen. Journal of Endocrinology (1994) 143, 383–392

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.

Induction of Cytochrome P-450-linked Monooxygenase System in Rat Liver Microsomes by Xiao-Chaihu-Tang

1996 ◽  
Vol 24 (02) ◽  
pp. 143-151 ◽  
Author(s):  
Taira Ohnishi ◽  
Hirohito Yoneyama ◽  
Tatushichiro Hamamoto ◽  
Toshihiko Ishida ◽  
Jirou Takahara ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
The Other ◽  
Female Rats ◽  
Male Rats ◽  
Monooxygenase System ◽  
Rat Liver Microsomes ◽  
Female Rat ◽  
Metabolic Rates ◽  
Cytochrome P 450

The administration of Xiao-Chaihu- Tang (TJ-9) for 2 weeks induced a 25% increase in the content of cytochrome P-450 in female rat liver microsomes, while the content in male rats remained unchanged. The enzymatic activities toward various xenobiotics were stimulated in female rats, the levels being in the range of 125-250% of those in the control rats. Among these xenobiotics, the metabolic rates for substrates of cytochrome P-450 2El were significantly enhanced in female rats. On the other hand, the activities toward various xenobiotics in male rats were unchanged. When 3-methylcholanthrene was given to rats for a week, the augmentation of cytochrome P-450 content and the stimulation ofxenobiotic metabolism were observed. However, co-administration ofTJ-9 did not alter the effect of 3-methylcholanthrene described above.

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

EFFECT OF α-MELANOCYTE-STIMULATING HORMONE AND OVARIAN STEROIDS ON PREPUTIAL GLAND FUNCTION IN THE FEMALE RAT

1981 ◽  
Vol 90 (1) ◽  
pp. 53-58 ◽  
Author(s):  
S. M. DONOHOE ◽  
A. J. THODY ◽  
S. SHUSTER
Keyword(s):  
Pituitary Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Preputial Gland ◽  
Melanocyte Stimulating Hormone ◽  
Experienced Male ◽  
Hypophysectomized Rats ◽  
Gland Function ◽  
Preputial Glands

Sexually experienced male rats were used to test the attractiveness of preputial gland odours of female rats. The male rats showed a clear preference for the preputial gland odours of hypophysectomized females given oestradiol benzoate (OB) for 3 or 8 days to those of control rats. Progesterone treatment had no effect on the attractiveness of the preputial gland odours of OB-treated hypophysectomized female rats. Administration of α-MSH for either 3 or 8 days, on the other hand, increased the attractiveness to male rats of preputial gland odours of OB-treated hypophysectomized females and the presence of progesterone produced no further change. When administered alone α-MSH had no effect on the attractiveness of the preputial gland odours. Other pituitary hormones, such as ACTH and prolactin, had no effect on the attractiveness of preputial gland odours of OB-treated hypophysectomized rats when administered for 3[unk]days. An increase in preputial gland size was only seen when OB, progesterone and α-MSH were administered together. It would appear that no relationship exists between the size of the preputial glands and their ability to attract male rats. It is concluded that, while α-MSH and progesterone may be important in controlling growth of the preputial glands, an interaction between α-MSH and oestrogen is more important for regulating the production of sex attractants by the preputial glands.

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