Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice

Hong, Jun-Yan; Ning, Shu; Ma, Bing-Li; Lee, Mao-Jung; Pan, Jingshun; Yang, Chung S.

doi:10.1016/0003-9861(90)90422-u

Cited by 31 publications

(5 citation statements)

References 33 publications

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“…On the other hand, Hong et al (1990) reported that hypophysectomy has no major e ect on the amount of CYP2E1. Therefore, in contrast to rat, mouse CYP2E1 does not seem to be altered by decreased growth hormone secretion even though the streptozotocininduced diabetic ddY mouse showed low growth hormone levels (Murao et al 1995).…”

Section: Discussionmentioning

confidence: 97%

Different expression of hepatic and renal cytochrome P450s between the streptozotocininduced diabetic mouse and rat

et al. 2001

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1. Since limited information is available about alterations of cytochrome P450 levels in diabetic animals other than rat, expression of P450s in the liver and kidney of the streptozotocin (STZ)-induced diabetic mouse was investigated. 2. The mRNA levels of CYP2B10, 3A11, 4A10 and 4A14 in the liver were increased in the STZ-induced diabetic mouse of both sexes. The CYP2B9 mRNA level was increased in the liver of the male diabetic mouse. These alterations were observed even at 2 weeks after administration. Insulin treatment restored these changes. The findings were consistent with changes reported in rat. 3. The levels of hepatic CYP1A2 and 2E1 and renal 2E1 and 4A did not change in the diabetic mouse at any time-point examined. No changes were seen in CYP2A- or 2C-related proteins in the diabetic mouse. These findings were in contrast to those in rat. 4. The results indicate that mouse P450s respond to insulin-dependent diabetes mellitus differently from those of the rat, and suggest that the expression of P450s in diabetes is not generally the same across animal species.

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Section: Discussionmentioning

confidence: 97%

Different expression of hepatic and renal cytochrome P450s between the streptozotocininduced diabetic mouse and rat

et al. 2001

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“…GH is a major endocrine factor modulating Cyp2e1 expression in the liver (11,28,42,71,76,77,80), with a determinant role in the sexual dimorphism observed in the expression of numerous genes (45,74,76). GH binds to the GH receptor on the cell membrane and activates signaling pathways including that by the GH pulse-activated transcription factor STAT5b (27), which is essential for the liver sexual dimorphism (14).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies revealed that pituitary hormone depletion by hypophysectomy resulted in Cyp2e1 upregulation in the liver of rats and GH supplementation normalized Cyp2e1 expression to constitutive levels by suppressing Cyp2e1 transcription (11,28,70,71,80). It is of interest to note that sex steroid hormones target complex regulatory dynamics including GH secretion.…”

mentioning

confidence: 99%

Sex steroid hormones regulate constitutive expression ofCyp2e1in female mouse liver

Konstandi

Cheng

Gonzalez

2013

American Journal of Physiology-Endocrinology and Metabolism

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Konstandi M, Cheng J, Gonzalez FJ. Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver. Am J Physiol Endocrinol Metab 304: E1118 -E1128, 2013. First published April 2, 2013; doi:10.1152/ajpendo.00585.2012.-CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17␤-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1␣, ␤-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states.Cyp2e1; 17␤-estradiol; progesterone; estrous cycle; mice PITUITARY HORMONES, in particular, growth hormone (GH), are considered critical in Cyp2e1 regulation. Previous studies revealed that pituitary hormone depletion by hypophysectomy resulted in Cyp2e1 upregulation in the liver of rats and GH supplementation normalized Cyp2e1 expression to constitutive levels by suppressing Cyp2e1 transcription (11,28,70,71,80). It is of interest to note that sex steroid hormones target complex regulatory dynamics including GH secretion. On the one hand, they augment GH-secretory burst by amplifying feedforward [via both GH-releasing hormone, GH-releasing peptide(s)] and on the other hand they attenuate feedback (imposed by somatostatin and GH). The role of testosterone is less clear (49,67). Previous studies in humans and experimental animals presented contradictory findings regarding sex differentiation in CYP2E1 constitutive expression and the role of sex steroid hormones in this regulation (5,11,29,33,34,59). This contradiction is probably du...

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“…Hypophysectomy and triiodothyronine increase CYP2E1 protein and mRNA levels in contrast to insulin which lowers them (89,95). In primary rat hepatocyte cultures, glucagon lowered CYP2E1 levels by accelerating turnover of the CYP2E1 protein by a cyclic AMP-dependent process (96).…”

Section: Induction and Regulation Of Cyp2e1mentioning

confidence: 99%

CYP2E1 and oxidative liver injury by alcohol

Cederbaum

2008

Free Radical Biology and Medicine

662

534

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Ethanol-induced oxidative stress appears to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway appears to be the induction of cytochrome P450 2E1 (CYP2E1) by ethanol. CYP2E1 metabolizes and activates many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide, and in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This Review Article summarizes some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of cell lines developed to constitutively express CYP2E1 in assessing the actions of CYP2E1. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help to understand the actions of CYP2E1 and its role in alcoholic liver injury.

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Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice

Cited by 31 publications

References 33 publications

Different expression of hepatic and renal cytochrome P450s between the streptozotocininduced diabetic mouse and rat

Different expression of hepatic and renal cytochrome P450s between the streptozotocininduced diabetic mouse and rat

Sex steroid hormones regulate constitutive expression ofCyp2e1in female mouse liver

CYP2E1 and oxidative liver injury by alcohol

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