scholarly journals Steroid glucuronyltransferases of rat liver. Properties of oestrone and testosterone glucuronyltransferases and the effect of ovariectomy, castration and administration of steroids on the enzymes

1977 ◽  
Vol 162 (3) ◽  
pp. 545-556 ◽  
Author(s):  
G S Rao ◽  
G Haueter ◽  
M L Rao ◽  
H Breuer
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Specific Activity ◽  
Normal Activity ◽  
Competitive Inhibitor ◽  
Female Rats ◽  
Male Rats ◽  
Prolonged Treatment ◽  
Microsomal Preparation ◽  
Ionic Detergent

1. Microsomal preparations from rat liver, kidney and intestine were tested for UDP-glucuronyltransferase activity by using oestrone, oestradiol-17 beta, oestriol, testosterone, cortisol, cortisone, corticosterone, aldosterone, tetrahydrocortisol and tetrahydrocortisone as substrates. The microsomal preparation from the liver glucuronidated oestrone, oestradiol-17 beta and testosterone. 2. The specific activity of the enzyme was significantly higher in livers from female rats than in those from male rats. 3. Testosterone was actively glucuronidated by both sexes. Cortisol, cortisone, corticosterone, aldosterone, tetrahydrocortisol and tetrahydrocortisone were not glucuronidated by any of the three tissues. 4. The non-ionic detergent Lubrol WX activates liver microsomal UDP-glucuronyltransferase 2-3-fold with oestrone and testosterone as substrates. 5. Oestrone glucuronyltransferase was inhibited by oestradiol-17 beta, predominantly competitively and by testosterone non-competitively. Bilirubin was a non-competitive inhibitor of oestrone glucuronidation. p-Nitrophenol had no effect. 6. Oestrone glucuronyltransferase could not be stimulated by either acute or prolonged treatment of animals with phenobarbital, whereas a single dose of 3-methylcholanthrene led to a moderate stimulation. 7. Ovariectomy leads to a 56% decrease in oestrone glucuronyltransferase activity; administration of oestradiol-17 beta induces the enzyme to normal activity after 12 days, and after 15 days the activity is twice the control value. Actinomycin D and cycloheximide block the oestradiol-17 beta-induced increase in enzyme activity. 8. Castration has no effect on the activity of testosterone glucuronyltransferase, nor does administration of testosterone influence enzyme activity. The results provide strong evidence for the existence of multiple steroid glucuronyltransferases in the liver of the rat.

scholarly journals The effect of phenobarbital on the submicrosomal distribution of uridine diphosphate glucuronyltransferase from rat liver

1970 ◽  
Vol 117 (2) ◽  
pp. 319-324 ◽  
Author(s):  
G. J. Mulder
Keyword(s):  
Enzyme Activity ◽  
Density Gradient ◽  
Rat Liver ◽  
Microsomal Fraction ◽  
Specific Activity ◽  
Sucrose Density Gradient ◽  
Male Rats ◽  
Uridine Diphosphate ◽  
Triton X

1. The detergent Triton X-100 activates UDP glucuronyltransferase from rat liver in vitro six- to seven-fold with p-nitrophenol as substrate. The enzyme activity when measured in the presence of Triton X-100 is increased significantly by pretreatment of male rats with phenobarbital for 4 days (90mg/kg each day intraperitoneally). If no Triton X-100 is applied in vitro such an increase could not be shown. In all further experiments the enzyme activity was measured after activation by Triton X-100. 2. The Km of the enzyme for the substrate p-nitrophenol does not change on phenobarbital pretreatment. 3. When the microsomal fraction from the liver of untreated rats is subfractionated on a sucrose density gradient, 47% of the enzyme activity is recovered in the rough-surfaced microsomal fraction, which also has a higher specific activity than the smooth-surfaced fraction. 4. Of the increase in activity after the phenobarbital pretreatment 50% occurs in the smooth-surfaced fraction, 19% in the rough-surfaced fraction and 31% in the fraction located between the smooth- and rough-surfaced microsomal fractions on the sucrose density gradient. 5. The latency of the enzyme in vitro, as shown by the effect of the detergent Triton X-100, is discussed in relation to the proposed heterogeneity of UDP glucuronyltransferase.

GONADAL FACTORS REGULATING THE ACTIVITY OF THE 17β-HYDROXYSTEROID OXIDOREDUCTASE IN RAT LIVER

1974 ◽  
Vol 77 (4) ◽  
pp. 727-736 ◽  
Author(s):  
H. Thaler-Dao ◽  
H. Breuer
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Adult Female ◽  
Female Rats ◽  
Male Rats ◽  
Steroid Metabolism ◽  
Normal Male ◽  
Normal Female ◽  
Cytosol Fraction ◽  
Key Enzyme

ABSTRACT The activity of the 17β-hydroxysteroid oxidoreductase (17β-HSOR), catalysing the oxidoreduction of oestradiol-17β and oestrone, has been studied in the cytosol fraction of rat liver under various conditions. The activity of the enzyme increased during maturation and reached a plateau at 100 days in females and at 180 days in males. In adult male rats, the activity of the 17β-HSOR was about 60% higher than in adult female rats. When female animals were castrated, the development of enzyme activity was similar to that observed in male rats; there was no difference in enzyme activity between adult castrated female rats and normal male rats. In normal female rats the activity of the 17β-HSOR was high during metoestrus and dioestrus, and low during pro-oestrus and oestrus. These findings show that oestrogens have a repressing effect on the activity of a key enzyme of steroid metabolism in rat liver.

Influence of age, adrenalectomy, and corticosteroids on hepatic transaminase activity

1961 ◽  
Vol 201 (2) ◽  
pp. 271-275 ◽  
Author(s):  
Homer R. Harding ◽  
Fred Rosen ◽  
Charles A. Nichol
Keyword(s):  
Rat Liver ◽  
Specific Activity ◽  
Fetal Liver ◽  
Alanine Transaminase ◽  
Female Rats ◽  
Male Rats ◽  
Transaminase Activity ◽  
Fetal Rat ◽  
Hepatic Transaminase ◽  
Fetal Rat Liver

The activity of alanine-α-ketoglutarate transaminase in rat liver was found to be uniform during the first 6 weeks of life, increasing thereafter until at 48 weeks of age the specific activity was seven times greater than in the immature rat. In rats varying in age from 4 days to 24 weeks, treatment with 1 mg of cortisol for 4 days resulted in significant increases in hepatic alanine transaminase activity. Female rats were less responsive to cortisol treatment than were males. Fetal rat liver had significantly lower alanine transaminase activity than did newborn animals and the activity of this enzyme in fetal liver was not altered by cortisol treatment. Adrenalectomy of adult male rats, but not immature male rats, resulted in a decrease in alanine transaminase activity; after 48 hr, enzyme activity was depressed to levels found in unoperated immature rats. The sensitivity of the adrenalectomized animals to cortisol administration was comparable to that of intact animals. In contrast, the aspartate-α-ketoglutarate transaminase was not appreciably altered following cortisol treatment or adrenalectomy and did not increase with age.

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.

Abstract WP153: Post-Stroke Physical Exercise Improves Cognition in Middle-Aged Female Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sharnikha Saravanan ◽  
Weizhao Zhao ◽  
Kunjan R Dave ◽  
Miguel A Perez-Pinzon ◽  
Ami P Raval
Keyword(s):  
Enzyme Activity ◽  
Physical Exercise ◽  
Cognitive Decline ◽  
Fear Conditioning ◽  
Enzyme Activities ◽  
Female Rats ◽  
Male Rats ◽  
Mitochondrial Enzyme ◽  
Post Stroke ◽  
Activity Measurements

Background: A woman’s risk of a stroke increases exponentially following the onset of menopause, andpost-stroke cognitive decline is a significant consequence of stroke survivors. Our earlier study demonstrated that physical exercise (PE) reduced post-stroke brain injury and improved cognitive functions in male rats. The focus of our study is on the improvement of post-stroke cognitive function in female rats. Methods: Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO; 90 min) and randomly assigned to either PE or sham-PE groups. After 3-5 days, rats underwent sham-PE (0m/min speed) or PE (15m/min speed) for 30 mins either every day (continuous) or alternate day for five times on treadmill. The rats that underwent the alternate day paradigm were treated with ER-β agonist (DPN; 1mg/kg) or vehicle-DMSO immediately following PE/sham-PE sessions to determine the synergistic effect. Twenty-one days after the last PE/sham-PE, rats were tested for hippocampal-dependent contextual fear conditioning and freeze time was measured. Rat brains were processed for histology and infarct area was measured with MCID software. From a separate cohort of rat subjected to PE or sham-PE, brain tissue was harvested for various biochemical assays and mitochondrial enzyme activity measurements. Results: Post-tMCAO continuous PE did not reduce ischemic damage. However, alternate PE regimen with or without ER-β agonist reduced infract volume by 20% (p < 0.05) and 23% (p < 0.05), respectively as compared to no-PE. Similarly, alternate PE showed increased freezing on the second day of fear conditioning by 15% (p < 0.05), indicating improved spatial memory. Individual mitochondrial complex I, II, III and IV enzyme activity measurements demonstrated significant improvement in complex III-IV enzyme activities in the alternate PE treated group as compared to sham-PE. Conclusion: An alternate day PE paradigm and ER-β activation improves post-stroke mitochondrial enzyme activities and cognition in reproductively senescent female rats. Future studies delineating underlying mechanism could help identify therapies to prevent/reduce cognitive decline in menopausal female stroke patients.

Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone.

1977 ◽  
Vol 232 (5) ◽  
pp. E522
Author(s):  
M Lis ◽  
R Boucher ◽  
M Chrétien ◽  
J Genest
Keyword(s):  
Growth Hormone ◽  
Angiotensin Ii ◽  
Specific Activity ◽  
Specific Binding ◽  
Combined Treatment ◽  
Submaxillary Gland ◽  
Female Rats ◽  
Male Rats ◽  
Angiotensin I ◽  
Sharp Drop

Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland.

Androgens and estrogens affect hepatic bile acid sulfotransferase in male rats

1985 ◽  
Vol 248 (6) ◽  
pp. G639-G642 ◽  
Author(s):  
R. B. Kirkpatrick ◽  
N. M. Wildermann ◽  
P. G. Killenberg
Keyword(s):  
Bile Acid ◽  
Chemical Structure ◽  
Specific Activity ◽  
Estrogen Treatment ◽  
Female Rats ◽  
Male Rats ◽  
Hepatic Bile ◽  
Similar Treatment ◽  
Untreated Female ◽  
Varied Chemical

The effect of estrogens and androgens on hepatic glycolithocholate sulfotransferase activity was studied in male rats. Significant increases in specific activity were noted following treatment of rats for 21 days with 17 beta-estradiol, 17 alpha-ethynylestradiol, and the nonsteroidal estrogen agonists nafoxidine, tamoxifen, and diethylstilbestrol. Similar treatment of male rats with 5 alpha-dihydrotestosterone, hydrocortisone, norethindrone, and prolactin did not affect activity. To further assess the effect of androgens, male rats were castrated. Glycolithocholate sulfotransferase activity increased fivefold by 14 days after castration. Treatment of castrated rats with 5 alpha-dihydrotestosterone prevented the increase and maintained activity at the level of sham-operated animals. Castrated animals exhibited an additional increment in activity following treatment with 17 alpha-ethynylestradiol: specific activity in these animals rose to levels comparable with those measured in untreated female rats. These data suggest endogenous androgens maximally suppress hepatic glycolithocholate sulfotransferase activity in male rats. The data also indicate that activity is stimulated by estrogenic compounds of varied chemical structure and that stimulation is not solely due to suppression of androgen release by the testes as a consequence of estrogen treatment.

FACTORS INFLUENCING THE EXCRETION OF A FAT-MOBILIZING SUBSTANCE IN THE URINE OF RATS

1966 ◽  
Vol 44 (1) ◽  
pp. 95-101 ◽  
Author(s):  
J. R. Beaton ◽  
A. J. Szlavko ◽  
J. A. F. Stevenson
Keyword(s):  
Body Weight ◽  
Sex Difference ◽  
Specific Activity ◽  
Young Male ◽  
Total Activity ◽  
Female Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Adult Rats ◽  
Factors Influencing

The effect of various factors on excretion of a lipid-mobilizing activity in FMS IA (anorexigenic) and in FMS IB (fat-mobilizing) by the fasting rat has been investigated. During fasting, the greatest excretion of such activity in FMS IA and FMS IB occurred in the first 24 hours and diminished thereafter up to 72 hours; and the specific activity of FMS IB was greatest in the first 24 hours whereas that of FMS IA was constant throughout. The hypothalamicobese rat excretes FMS IA and FMS IB in greater than normal amounts. The alloxan-diabetic rat excretes less total activity of FMS IA and IB than do control animals. Young male rats excrete greater amounts of FMS IB, but not of FMS IA, than do adult rats, the greatest excretion per 100 g body weight being observed at approximately 37 days of age. At 27 days of age (prepuberty), male rats excreted a greater total activity of FMS IB but not of FMS IA than did female rats. At 90 days of age (post-puberty), there was no apparent sex difference in the amount of total activity of FMS IB excreted per rat, but when expressed per 100 g body weight, females excreted more FMS IB than did males.

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