Effect of Steroidal Sex Hormones on the Sex-Related Differences in the Hepatic Activities of
            <i>γ</i>
            -Glutamyltranspeptidase Glutathione S-Transferase and Glutathione Peroxidase in Rats

Isobe, Takashi; Satoh, Takeo; Ono, Shoichiro; Iwashita, Keiko; Hosokawa, Masakiyo; Ueno, Keisuke; Kitagawa, Haruo

doi:10.1016/s0022-5347(17)48972-5

Cited by 16 publications

(13 citation statements)

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“…Ovariectomized rats have enhanced GST levels. Estradiol increases GGT activity in castrated males [184]. Sex-related effects during hepatocarcinogenesis have also been reported [138,167].…”

Section: Regulation Of Ggt and Pgst During Hepatocarcinogenesismentioning

confidence: 98%

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Hendrich

Pitot

1987

Cancer Metast Rev

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Enzymes of glutathione metabolism, particularly gamma-glutamyltransferase (GGT) and glutathione S-transferase (GST), play a role in multistage hepatocarcinogenesis. The enhanced expression of these enzymes in preneoplastic altered hepatic foci, nodules, and hepatocellular carcinomas has been demonstrated after treatment with a variety of initiating and promoting agents. Glutathione is necessary for the detoxification of xenobiotics and carcinogens and for cell replication. Induction of GGT in altered hepatocytes may permit these cells to utilize extracellular glutathione to preserve their internal glutathione levels. GST induction allows glutathione utilization for the protection of the altered hepatocyte in an environment of exposure to xenobiotics, such as promoting agents. Thus, the combined effects of GGT and GST, in a toxic environment, may provide for the enhanced proliferation observed in preneoplastic hepatocytes. New clinical and research opportunities may involve the use of GGT and the placental isozyme of GST (PGST) as markers of preneoplasia and neoplasia in humans. Many factors, such as hormones, diet, and exposure to initiating and promoting agents, influence GGT and GST expression. The recent cloning of cDNAs to GGT and PGST offers opportunities for the study of factors involved in the genetic expression of these two enzymes. Coupled with the use of hepatocyte culture and transplantation, the factors involved at the molecular level in the creation of hepatocellular neoplasia may be discovered.

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“…Ovariectomized rats have enhanced GST levels. Estradiol increases GGT activity in castrated males [184]. Sex-related effects during hepatocarcinogenesis have also been reported [138,167].…”

Section: Regulation Of Ggt and Pgst During Hepatocarcinogenesismentioning

confidence: 98%

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Hendrich

Pitot

1987

Cancer Metast Rev

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“…Experiment 1 was done in early May, at the beginning of the spawning season, when the fish were gravid. Both GST and UGT activity can be affected either up-or down-regulated by hormonal expression in mammals Igarashi et al, 1984, steroid hormones; Masmoudi et a!., 1996, thyroxin and in fish Koivusaari et a!., 1981;Sikoki et a!., 1989;Leaver and George, 1996. Experiment 2 was conducted in early March, prior to the beginning ofthe spawning season, with gonadally regressed fish.…”

Section: Udp Glucuronosvl Transferase Ugt Activity: the Protocol Descmentioning

confidence: 99%

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

Bello¹

1999

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New Bedford Harbor NBH, MA, is contaminated with halogenated aromatic hydrocarbons HAH including some potent aryl hydrocarbon receptor AhR agonists. To determine ifFundulus heterocitus from NBH have developed resistance to HAll, we examined the inducibility of cytochrome P4501A1 CYP1A1 in fish from NBH and Scorton Creek SC, reference site. Despite higher PCB concentrations in NBH than in SC fish --1 500-fold -CYP1A1 expression, in most tissues, was not higher in NBH fish than in SC fish. Glutathione S-transferase GST and UDP-glucuronosyltransferase UGT activities were higher in NBH fish than in SC fish, but only when fish were collected during different seasons. GST activity was higher in the intestines ofNBH fish than in any other tissue.2,3,7,8-Tetrachlorodibenzoftiran TCDF induced CYP1A1 expression, in all tissues examined, in SC fish. In contrast, NBH fish showed little CYP1A1 induction by any measure, in any tissue. Hepatic GST activity was induced only in male NBH fish. Hepatic UGT activity showed no relationship to treatment in fish from either site.2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD and J3-naphthoflavone BNF induced CYP1A1 activity to the same level in primary cultures ofhepatocytes from either SC orNBH fish. However, hepatocytes from NBH fish were 14-fold less sensitive to TCDD and 3-fold less sensitive to BNF than hepatocytes from SC fish.To examine the heritability ofresistance, NBH and SC F1 fish were treated with 3H-TCDD or BNF. 3H-TCDD induced CYP1A1 expression only in SC F1 fish. BNF induced CYP1A1 expression in both SC and NBH F1 fish. There was no significant difference in hepatic 3H-TCDD concentrations between SC and NBH F1 fish.Hepatic AhR content, as measured by photoaffinity labeling with '25I-N3Br2DD, was lower in NBH fish than in SC fish and lower in males than in females. After 90 days in captivity, the sex difference persisted, but the site difference did not. TCDF induced hepatic AIIR content in NBH F1 fish.These results indicate that NBH Fundulus have developed a pre-translational, systemic, heritable resistance to HAHs. These findings suggest that an alteration in the AIIR pathway is responsible for this resistance; this is the subject ofcontinuing research. Next, I owe more than I can say to my thesis advisor and friend Mark Hahn. He was always available whenever I needed to consult on ideas, was endlessly tolerant of the bizarre hours I kept, and fostered a truly enjoyable work environment.Bruce Woodin was an ever accommodating and delightful person to work with. I want to thank him for all ofhis help with dissections, his enlightening field trips, and for generally making my time here that much more enjoyable. I thank Diana Franks for her work with the primary culturing of the Fundulus hepatocytes, for her help with fish care and for generally helping to make my life a little easier. Diane Nacci, Ken Rocha, and the EPA laboratory in Narragansette for kindly providing fish. Diane also for her help during the planning stages ofthis work and her willingness to exchange r...

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“…In the ovaries of immature rats treated with E 2 , the total GST activity was elevated (7). Igarashi et al (30) detected reduced immunoreactivity and activity of total GST in the liver after E 2 administration but not in the expression of the ␣-class. Coecke et al (11) observed that the treatment of hepatocytes with E 2 increased the content of the ␣-class subunits A1 and A2 of GST.…”

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confidence: 96%

“…Less is known about GST regulation by hormones. Adrenocorticotrophic hormone (39), glucocorticoids (19, 33), growth hormones (54), thyroid hormones (TH) (6,11,31), and sex steroids (7,25,30) are able to modulate GST.Thyroid hormones, including thyroxine (T 4 ) and triiodothyronine (T 3 ), are essential during embryonic development and play critical roles in several physiological processes in adult organisms (36). It is agreed that most of the TH effects are mediated by nuclear action via a superfamily of ligand-modulated transcription factors that modify target gene transcription (36).…”

mentioning

confidence: 99%

Thyroid hormone and estradiol have overlapping effects on kidney glutathioneS-transferase-α gene expression

Faustino

Almeida

Pereira

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Class GST (Gsta) represents an essential component of cellular antioxidant defense mechanisms in both the liver and the kidney. Estrogens and thyroid hormones (TH) play central roles in animal development, physiology, and behavior. Evidence of the overlapping functions of thyroid hormones and estrogens has been shown, although the molecular mechanisms are not always clear. We evaluated an interaction between TH and estradiol in regulating kidney Gsta expression and function. First, we observed that female mice expressed greater amounts of Gsta compared with males and showed an opposite pattern of expression in TR␤ knock-in mice. To further investigate these sex differences, hypothyroidism was induced by a 5-propyl-2-thiouracil diet, and hyperthyroidism was induced by daily T 3 injections. Hypothyroidism increased kidney Gsta expression in male mice but not in female mice, indicating that sex hormones could be influencing the regulation of Gsta by thyroid hormones. To analyze this hypothesis, ovariectomized females were subjected to hypo-and hyperthyroidism, which led to a male profile of Gsta expression. When hypo-or hyperthyroid ovariectomized mice were treated with 17␤-estradiol benzoate, we were able to confirm that estradiol was interfering with TH modulation; Gsta expression is increased by T 3 when estradiol is present and decreased by T 3 when estradiol is absent. Using proximal tubule cells, we also showed that estradiol and T 3 worked together to modulate Gsta expression in an overlapping fashion. In summary, 1) the sex difference in the basal expression of Gsta impacts the detoxification process, 2) kidney Gsta expression is regulated by TH in males and females but in opposite directions, and 3) T 3 and estradiol interact directly in renal proximal cells to regulate Gsta expression in females.triiodothyronine; proximal tubule; cross-talk; ovariectomy; estrogen GLUTATHIONE S-TRANSFERASES (GSTs) are a superfamily of ubiquitous dimeric detoxification isoenzymes that conjugate many substrates to reduced glutathione (GSH), including several xenobiotic and endogenous electrophiles (26). Mammalian cytosolic GSTs represent the largest family of such transferases and have been divided into seven different classes (␣, , , , , , and ) (2, 27, 28). The ␣-class of GST (GST␣) is found in several organs, such as the liver, kidney, lung, stomach, and gonads, some of which exhibit sexual dimorphism (35). In the liver, the important role played by GST in cellular detoxification and in many other known functions has already been well described (26). However, in other tissues, the role of GST is still not well characterized.It has been established that GST␣ is a biomarker of renal toxicity that aids in the detoxification of endogenous and exogenous compounds and in drug metabolism (2). Renal GST isoforms are differentially expressed along nephron segments; expression also depends on species. In the human kidney, GST␣ is found predominantly in the proximal convoluted tubule, and low levels of GST␣ have been detected in the...

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Effect of Steroidal Sex Hormones on the Sex-Related Differences in the Hepatic Activities of γ -Glutamyltranspeptidase Glutathione S-Transferase and Glutathione Peroxidase in Rats

Cited by 16 publications

References 0 publications

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

Thyroid hormone and estradiol have overlapping effects on kidney glutathioneS-transferase-α gene expression

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