Hypothalamo-Pituitary Regulation of Cytochrome P-450<sub>15<i>β</i></sub>Apoprotein Levels in Rat Liver*

MacGeoch, C.; Morgan, Edward T.; Gustafsson, Jan‐Åke

doi:10.1210/endo-117-5-2085

Cited by 101 publications

(44 citation statements)

References 28 publications

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“…Sex hormones, via their effects on the pattern of pituitary growth hormone secretion, 12 play a major role in the regulation of this gene. 10,11,33 Thus, in this and other work, 11 estradiol administration to male rats induced expression of CYP2C12, and the combination of ovariectomy with testosterone administration abolished expression of CYP2C12 in female rats. 11,37 Using intact and hypophysectomized rats, it has been demonstrated that estradiol exerts its regulatory effect on CYP2C12 by stimulating the female continuous pattern of growth hormone release.…”

Section: Discussionsupporting

confidence: 71%

“…10,11,33 Thus, in this and other work, 11 estradiol administration to male rats induced expression of CYP2C12, and the combination of ovariectomy with testosterone administration abolished expression of CYP2C12 in female rats. 11,37 Using intact and hypophysectomized rats, it has been demonstrated that estradiol exerts its regulatory effect on CYP2C12 by stimulating the female continuous pattern of growth hormone release. 11,12 In the present study, serum estradiol concentrations were increased (and testosterone was decreased) in BDL female rats, and similar hormonal changes occur in male rats after BDL.…”

Section: Discussionsupporting

confidence: 71%

“…11,37 Using intact and hypophysectomized rats, it has been demonstrated that estradiol exerts its regulatory effect on CYP2C12 by stimulating the female continuous pattern of growth hormone release. 11,12 In the present study, serum estradiol concentrations were increased (and testosterone was decreased) in BDL female rats, and similar hormonal changes occur in male rats after BDL. 18 We reasoned, therefore, that estrogen accumulation in the presence of reduced levels of testosterone could be involved with the upregulation of CYP2C12 expression.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11][12][13][14] Biliary obstruction was produced in ether anesthetized rats by double-ligation and transection of the common bile duct, as described elsewhere. 18 Following surgery, animals were allowed to recover and were given free access to food (commercial rat chow) and water until required.…”

Section: Methodsmentioning

confidence: 99%

“…Sex hormones are involved with regulation of sexually dimorphic CYPs, principally via the effects on pituitary growth hormone secretion. 10,11 We therefore determined serum concentrations of estradiol and testosterone in BDL and sham-operated control female rats. As previously reported in male rats with BDL, 18 serum estradiol concentrations were 2.6-fold greater in BDL females than in controls (Table 2), while serum testosterone was reduced from low (mean, 0.7 pg/mL) values in sham-operated controls to undetectable levels after BDL.…”

Section: Effects Of Bdl On Serum Sex Hormone Concentrations and Bilementioning

confidence: 99%

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Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

et al. 1998

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Gender differences in hepatic sex steroid and drug metabolism result from hormonal regulation of specific cytochrome P450 genes (CYP). In male rats, bile duct ligation (BDL) is associated with down-regulation of the male-specific genes, CYP2C11 and CYP3A2, together with a decrease in serum testosterone levels and a two-to threefold increase in serum estradiol concentrations. We anticipated that if estrogen is responsible for down-regulation of male-specific CYPs in BDL male rats, the female-specific CYP2C12, which is not normally present in adult male rat liver, should be up-regulated. We examined this proposal by determining the profile of hepatic cytochrome P450 enzymes in female rats subjected to BDL, and by seeking evidence for expression of CYP2C12 in male rats that do not normally express this gene. In female rats killed 5 days after BDL, total cytochrome P450 content and NADPH-cytochrome P450-reductase (P450-reductase) were decreased to 74% and 58% of control, respectively. Microsomal enzyme activities attributable to CYP2A1, CYP2C6, and CYP2E1 were 50% to 60% of control, but ethylmorphine Ndemethylase, which in female liver is catalyzed by CYP2C12 and to a lesser extent CYP2C6, was significantly less affected (81% of control). Likewise, levels of CYP2C6 and P450-reductase proteins were decreased in proportion to the corresponding enzyme activities (50% to 60%), while CYP2C12 protein (and mRNA levels) were not altered in BDL female rat liver. In sham-operated male rats, transcripts for CYP2C12 were rarely detected, but mRNA levels rose to appreciable levels within 24 hours of BDL, and CYP2C12 protein was expressed in hepatic microsomes of BDL male rats. Administration of estradiol to male rats produced a similar elevation of CYP2C12 mRNA, to values Ϸ40% of female rats. It is concluded that CYP2C12 is up-regulated in male rats with cholestasis caused by BDL, while CYP2C12 protein is preserved in female rats when other microsomal proteins are decreased. These changes may be related to the increase in serum estradiol levels that result from altered hepatic steroid metabolism. The results demonstrate that activities of individual drug-metabolizing enzymes in liver disease can be determined by dysregulation of the constitutive expression of hepatic CYP genes. (HEPATOLOGY 1998;28:624-630.)Hepatic cytochrome P450 (P450) proteins play an important role in the biotransformation of many foreign compounds and physiological substrates, including drugs, procarcinogens, bile acids, and steroid hormones. The broad range of substrate specificities is explained by the existence of multiple genes (CYPs) for the cytochromes P450, each of which encodes an individual protein that catalyzes a relatively specific range of enzyme reactions. In rat liver, for instance, the activities of several P450s are indicated by the regio-and stereo-specific hydroxylation of C19-steroid hormones, including testosterone and progesterone. 1-6 Rats exhibit striking sex differences in hepatic drug and steroid metabolism, and this is accounted fo...

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Effects Of Bdl On Serum Sex Hormone Concentrations and Bilementioning

confidence: 99%

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Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

et al. 1998

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Sex Differences in Drug Metabolism

Chang

Waxman

2012

Encyclopedia of Drug Metabolism and Interactions

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Sex differences in drug metabolism are recognized as a major determinant of sex differences in pharmacokinetics and an important contributor to interindividual differences in drug metabolism and, in some cases, drug action. Sex differences in human drug metabolism have also been observed with a variety of drugs. The biochemical basis of sex differences in hepatic drug metabolism was largely unknown until the 1980s when it was discovered that the expression of many drug‐metabolizing enzymes, including several members of the cytochrome P450 (CYP) superfamily, is sex dependent in rat and mouse liver. Well‐studied examples include rat enzymes CYP2C11, which is male specific in its expression, and CYP2C12 (female specific) and CYP2A1 (female predominant). The major gonadal hormones, testosterone and estradiol, regulate the sex‐dependent expression of rat hepatic CYP enzymes indirectly, through their effects on the hypothalamus and its regulation of the sexually dimorphic, ultradian rhythm of pituitary growth hormone (GH) secretion, which ultimately dictates the sex‐dependent patterns of expression of these CYPs and certain other drug‐metabolizing enzymes. In male rats, the intermittent, pulsatile pattern of GH secretion stimulates the expression of male‐specific liver enzymes, whereas the more continuous pattern of GH release in females suppresses the expression male‐specific enzymes while inducing female‐specific enzymes. The current view is that the transcription factors STAT5b and HNF4α coordinately regulate the action of GH and its resultant effect on the sex‐dependent expression of hepatic CYP genes and thus provide a molecular basis for sex differences in drug metabolism.

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The influence of thermal treatment on color response of wood materials

Aydemir

Gündüz

Ozden

2010

Color Research & Application

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In this study, the influence of thermal treatment on color changes of six different wood materials was investigated. Test specimens were subjected to three different temperatures (160, 180, and 200°C) and durations (3, 5, and 7 h). The data obtained were analyzed using variance analysis, and then the statistical analysis of Tukey's test was conducted. After this treatment, the results showed that the color values of the six wood materials changed significantly. It was determined that L* (lightness) values decreased; the minimum change in L* was ∼4% for Juniper wood, and the maximum change in L* was ∼64% for Beech wood. The values of a* (red coordinate) and b* (yellow coordinate) showed varying levels of increase when the heat treatment conditions were 160°C for 3 to 7 h (not including Cherry wood), but the values began to decrease slowly after treatment at 160°C for 5 h. The ratios of the minimum and maximum color change in a* and b* were determined at 180°C for 3 h in Plane wood, 200°C for 5 h in Hazelnut wood, and 160°C for 3 h and 200°C for 7 h in Beech wood. As temperature and duration were increased, the minimum total color change (ΔE ab*) was ∼3.5% for 160°C at 3 h in Cypress wood, and the maximum total color change (ΔE ab*) was ∼50% for 200°C at 7 h in Cypress wood. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2010

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Hypothalamo-Pituitary Regulation of Cytochrome P-450_15βApoprotein Levels in Rat Liver*

Cited by 101 publications

References 28 publications

Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

Sex Differences in Drug Metabolism

The influence of thermal treatment on color response of wood materials

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Hypothalamo-Pituitary Regulation of Cytochrome P-45015βApoprotein Levels in Rat Liver*

Cited by 101 publications

References 28 publications

Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

Effects of bile duct ligation on hepatic expression of female-specificCYP2C12 in male and female rats

Sex Differences in Drug Metabolism

The influence of thermal treatment on color response of wood materials

Contact Info

Product

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Hypothalamo-Pituitary Regulation of Cytochrome P-450_15βApoprotein Levels in Rat Liver*