scholarly journals Growth hormone- and testosterone-dependent regulation of glutathione transferase subunit A5 in rat liver

1998 ◽  
Vol 332 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Louise STAFFAS ◽  
Elizabeth M. ELLIS ◽  
John D. HAYES ◽  
Bo LUNDGREN ◽  
Joseph W. DePIERRE ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Rat Liver ◽  
Hormonal Regulation ◽  
Glutathione Transferase ◽  
Affinity Purification ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Male And Female Rats

The class Alpha glutathione S-transferase (GST) subunit A5 is expressed in the livers of young male and female rats. After sexual maturation, this protein is no longer detectable in the livers of male rats, but is still expressed in female rats. We have previously demonstrated that the sexually dimorphic secretion of growth hormone regulates the levels of certain class Mu GSTs in rat liver, and this study was designed to investigate the hormonal regulation of GSTA5. Control and hypophysectomized rats of both sexes were used to study the role of growth hormone in the regulation of hepatic GSTA5; and the influence of testosterone on the expression of this same subunit was investigated in intact females and castrated males. Liver cytosols were subjected to SDS/PAGE and immunoblotting using antibodies directed towards rat (r)GSTA5, and to affinity purification on glutathione–Sepharose followed by reverse-phase HPLC in order to quantify the relative levels of rGSTA1, A2, A3, A4, M1 and M2 subunits. These analyses revealed that the expression of rGSTA5 is, indeed, regulated by both growth hormone and testosterone.

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 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.

Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17β-d-glucuronide in rats

2002 ◽  
Vol 282 (6) ◽  
pp. E1245-E1254 ◽  
Author(s):  
Yasumasa Gotoh ◽  
Yukio Kato ◽  
Bruno Stieger ◽  
Peter J. Meier ◽  
Yuichi Sugiyama
Keyword(s):  
Gender Difference ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Hormonal Regulation ◽  
Organic Anion ◽  
Female Rats ◽  
Male Rats ◽  
Control Male ◽  
Male And Female Rats ◽  
Estradiol 17Β

The gender difference in the urinary excretion of estradiol-17β-glucuronide (E2-17βG) was examined in rats. The urinary clearance of E2-17βG was >250 times lower in male than in female rats. No such major gender difference was observed in its biliary excretion or metabolism in kidney homogenate. Both plasma protein binding and inulin clearance were comparable in male and female rats, suggesting that this gender difference cannot be explained by glomerular filtration. The urinary clearance with respect to the plasma unbound E2-17βG in male rats was <1% of the glomerular filtration rate, indicating its potential reabsorption by the kidney, and this increased to a level comparable with that found in female rats when dibromosulfophthalein was coinfused. A marked increase in E2-17βG urinary excretion was also observed in male rats that had undergone orchidectomy. Testosterone injections given to female rats reduced the urinary excretion to a level comparable with that of control male rats. The concomitant change in the expression of the gene product for organic anion-transporting polypeptide Oatp1, of which E2-17βG is a typical substrate, was found in the kidney membrane fractions after these treatments. These results suggest that urinary E2-17βG excretion is subject to hormonal regulation and that the large gender difference can be explained by regulation in Oatp1-mediated reabsorption.

Growth hormone responses to multiple injections of a fragment of human growth hormone-releasing factor in conscious male and female rats

1985 ◽  
Vol 106 (3) ◽  
pp. 281-289 ◽  
Author(s):  
R. G. Clark ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Human Growth ◽  
Female Rats ◽  
Male Rats ◽  
Normal Male ◽  
Male And Female ◽  
Gh Secretion ◽  
Male And Female Rats ◽  
Hormone Responses ◽  
Males And Females

ABSTRACT The GH responses to single i.v. injections of GH-releasing factor (GRF) in conscious male rats are highly variable. Although normal male rats show a pulsatile secretory pattern of GH with pulses occurring at intervals of 3–3·5 h, the peaks occur at different times in individual animals. We have compared the GH responses of young conscious male and female rats to multiple i.v. injections of 1 μg human (h) GRF1-29NH2. The peak GH responses occurred 3–5 min after hGRF1-29NH2 injection and were lower in female than in male rats. Both males and females responded uniformly to hGRF1-29NH2 injections given 180 min apart and the GH responses became entrained with no endogenous GH pulsing. Female rats produced consistent GH peaks in response to hGRF1-29NH2 injections at 90-min intervals, whereas male rats responded only to alternate injections, so that GH peaks occurred only every 180 min despite giving GRF every 90 min. When the frequency of hGRF1-29NH2 administration was increased to once every 40 min female rats again responded consistently to each injection. Male rats responded intermittently, being able to respond to two injections 40 min apart, after which they became refractory to hGRF1-29NH2. This cycle of varying sensitivity to GRF in male rats probably underlies their 3-hourly endogenous GH secretory rhythm. Female rats can respond uniformly to repeated GRF injections, consistent with their more continuous pattern of endogenous GH secretion. Introducing a pulse of 10 μg rat GH into a series of hGRF1-29NH2 injections did not induce refractoriness to hGRF1-29NH2, suggesting that GH does not itself desensitize the pituitary to GRF. Whether the different patterns of GH secretion in males and females result from different patterns of GRF and/or somatostatin secretion remains to be determined. J. Endocr. (1985) 106, 281–289

Potential adverse effects of oseltamivir in rats: males are more vulnerable than females

2011 ◽  
Vol 89 (9) ◽  
pp. 623-630 ◽  
Author(s):  
Wael M. El-Sayed ◽  
Mohamed Ali Al-Kahtani
Keyword(s):  
Adverse Effects ◽  
Protein Profile ◽  
Antiviral Drug ◽  
Thioredoxin Reductase ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Quinone Oxidoreductase ◽  
Male And Female Rats

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140–170 g). Oseltamivir was administered at 2.2 mg·kg–1·day–1 for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

Sex difference in growth hormone feedback in the rat

1990 ◽  
Vol 126 (1) ◽  
pp. 27-35 ◽  
Author(s):  
L. M. S. Carlsson ◽  
R. G. Clark ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Sex Difference ◽  
Female Rats ◽  
Male Rats ◽  
Constant Infusion ◽  
Physiological Control ◽  
Sampling System ◽  
Male And Female ◽  
Gh Secretion ◽  
Male And Female Rats

ABSTRACT Growth hormone inhibits its own secretion in animals and man but the mechanism for this inhibition is unclear: both stimulation of somatostatin release and inhibition of GH-releasing factor (GRF) release have been implicated. We have now studied the GRF responsiveness of conscious male and female rats under conditions of GH feedback induced by constant infusion of exogenous human GH (hGH). Intravenous infusions of hGH (60 μg/h) were maintained for 3 to 6 h whilst serial injections of GRF(1–29)NH2 (0·2–1 μg) were given at 45-min intervals. The GH responses were studied by assaying blood samples withdrawn at frequent intervals using an automatic blood sampling system. We have confirmed that male and female rats differ in their ability to respond to a series of GRF injections; female rats produced consistent GH responses for up to 13 consecutive GRF injections, whereas male rats showed a 3-hourly pattern of intermittent responsiveness. In female rats, multiple injections of GRF continued to elicit uniform GH responses during hGH infusions, whereas hGH infusions in male rats disturbed their intermittent pattern of responsiveness to GRF, and their regular 3-hourly cycle of refractoriness was prolonged. We suggest that this sex difference in GH feedback may be due to GH altering the pattern of endogenous somatostatin release differentially in male and female rats. Such a mechanism of GH autofeedback could be involved in the physiological control of the sexually differentiated pattern of GH secretion in the rat. Journal of Endocrinology (1990) 126, 27–35

scholarly journals Activities of Antioxidant and Detoxifying Enzymes in Rats after Lead Exposure

2008 ◽  
Vol 77 (3) ◽  
pp. 347-354 ◽  
Author(s):  
M. A. Alghazal ◽  
V. Lenártová ◽  
K. Holovská ◽  
A. Sobeková ◽  
M. Falis ◽  
...  
Keyword(s):  
Thiobarbituric Acid ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Sod Activity ◽  
Compensatory Response ◽  
Male And Female ◽  
Male And Female Rats ◽  
Enzyme Superoxide Dismutase ◽  
Gst Activity

The studies were undertaken to investigate the activity response of the antioxidant enzyme superoxide dismutase (SOD) and detoxifying enzyme glutathione-S-transferase (GST) of rats exposed to lead. Enzyme activities were determined in the liver, kidneys and heart of male and female rats that received 100 mg and 1000 mg of lead acetate per litre, respectively, in their drinking water for 18 weeks. Statistical analyses indicated differences related to the organs and to the sex of animals. Administration of lead evoked an increase of the SOD activity in the liver and kidneys both in male and female rats but only in the heart of female rats. GST activity decreased in the liver and heart of male rats, while this activity increased in the liver and heart of female rats. In kidneys, the lower lead dose resulted in a decrease of the GST activity in both groups but the higher dose evoked an increase of activity only in male rats. Thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, significantly increased in rats that were given the high lead dose, in the kidneys of male rats and in the heart of female rats. Most probably, the observed changes could be a compensatory response to different lead accumulation in the male and female organs and also the possible distinct mechanisms in ROS elimination.

Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related

2012 ◽  
Vol 90 (10) ◽  
pp. 1372-1379 ◽  
Author(s):  
John C. Passmore ◽  
John T. Fleming ◽  
Suresh C. Tyagi ◽  
Jeff C. Falcone
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Tyrosine Kinase Receptor ◽  
Middle Aged ◽  
Male And Female Rats ◽  
Age Related

Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)3, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.

EFFECTS OF ENDOCRINE MANIPULATIONS ON OESTROGEN BINDING IN CYTOSOLS FROM RAT SKELETAL AND PERINEAL MUSCLES

1980 ◽  
Vol 85 (3) ◽  
pp. 351-358 ◽  
Author(s):  
F. T. DIONNE ◽  
J. Y. DUBÉ ◽  
G. FRENETTE ◽  
R. R. TREMBLAY
Keyword(s):  
Binding Sites ◽  
Hormonal Regulation ◽  
Binding Capacity ◽  
Levator Ani ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Thigh Muscles ◽  
Male And Female Rats ◽  
Intact Rats

Hormonal regulation of cytosolic oestradiol-binding sites in the levator ani bulbocavernosus (LA/BC) muscles of male rats and in thigh muscles from male and female rats was investigated. Twenty-four hours after gonadectomy and/or adrenalectomy, the number of unoccupied oestradiol-binding sites was significantly increased in cytosols prepared from LA/BC muscles while these treatments had no effect on thigh muscles from male rats. Only a combination of both treatments led to a significant increase of oestradiol-binding sites in cytosols prepared from the thigh muscles of female rats when compared with those of intact rats at dioestrus. The number of oestradiol-binding sites in the thigh muscles of female rats was found to vary during the oestrous cycle with values significantly lower at pro-oestrus than at dioestrus. The increase in oestradiol-binding sites observed in cytosols prepared from muscles of adrenalectomized or gonadectomized plus adrenalectomized rats was prevented by an injection of corticosterone (3 mg, s.c.) at the time of surgery. Twenty-one days after gonad and/or adrenal ablation, the mean concentration of oestradiol-binding sites in the three tissues under study was higher than in these tissues from intact rats, and in some groups the levels of oestradiol-binding sites were significantly higher than they had been 24 h after the same surgical treatments. Muscles from male rats hypophysectomized for 28 days possessed levels of oestradiol-binding sites equivalent to male rats deprived of steroid hormones for 21 days. Dexamethasone treatment of male rats (100 μg/day for 14 days) led to a progressive decrease of oestradiol-binding sites of LA/BC and thigh muscles. This study has shown that adrenal and gonadal hormones exert both short- and long-acting repressive effects on the oestradiol-binding capacity of rat muscles.

scholarly journals Sex-related difference in the inductions by perfluoro-octanoic acid of peroxisomal β-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver

1989 ◽  
Vol 261 (2) ◽  
pp. 595-600 ◽  
Author(s):  
Y Kawashima ◽  
N Uy-Yu ◽  
H Kozuka
Keyword(s):  
Rat Liver ◽  
Octanoic Acid ◽  
Female Rats ◽  
Male Rats ◽  
Beta Oxidation ◽  
Related Difference ◽  
Male And Female Rats ◽  
Chain Acyl ◽  
Coa Hydrolase ◽  
Long Chain

Inductions by perfluoro-octanoic acid (PFOA) of hepatomegaly, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase were compared in liver between male and female rats. Marked inductions of these four parameters were seen concurrently in liver of male rats, whereas the inductions in liver of female rats were far less pronounced. The sex-related difference in the response of rat liver to PFOA was much more marked than that seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2′-(decamethylenedithio)diethanol (tiadenol). Hormonal manipulations revealed that this sex-related difference in the inductions is strongly dependent on sex hormones, namely that testosterone is necessary for the inductions, whereas oestradiol prevented the inductions by PFOA.

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