1
40
2
-
Text
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n/a
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
885-892
Issue
6
Volume
34
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Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Cholesterol 7-alpha-hydroxylase - Evidence For Transcriptional Regulation By Cholesterol Or Metabolic Products Of Cholesterol In The Rat
Publisher
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Journal of Lipid Research
Date
A point or period of time associated with an event in the lifecycle of the resource
1993
1993-06
Subject
The topic of the resource
bile-acid synthesis; bile fistula; bile-acid synthesis; Biochemistry & Molecular Biology; biosynthesis; cloning; enterohepatic circulation; enzyme; hepatic cholesterol; hepatocytes; hmg-coa reductase; liver microsomes; lovastatin; messenger-rna; mevalonate; stimulation
Creator
An entity primarily responsible for making the resource
Jones M P; Pandak W M; Heuman D M; Chiang J Y L; Hylemon P B; Vlahcevic Z R
Description
An account of the resource
Cholesterol 7alpha-hydroxylase, the rate-determining enzyme in the bile acid biosynthesis pathway, is regulated in a negative feedback manner by hydrophobic bile salts returning to the liver via the portal circulation. The role of cholesterol in the regulation of cholesterol 7alpha-hydroxylase and the interrelationship between the cholesterol and bile acid biosynthesis pathways remain controversial. The objective of the present study was to define the role of cholesterol in the regulation of cholesterol 7alpha-hydroxylase and determine the molecular level of its control. In order to avoid intestinal or intravenous administration of cholesterol, we manipulated the flow of cholesterol within the hepatocytes by decreasing cholesterol synthesis with lovastatin in bile fistula rats (bile acid synthesis is up-regulated), or by increasing cholesterol supply by administering mevalonate, a precursor of cholesterol, to rats with intact enterohepatic circulation (bile acid synthesis is normal). In the first series of studies, lovastatin was administered as a single intravenous bolus (10 mg/kg) to rats with chronic bile fistula and to rats with intact enterohepatic circulation (cholesterol and bile acid synthesis is normal). Three hours after lovastatin administration, cholesterol 7alpha-hydroxylase specific activity, enzyme mass, mRNA, and gene transcriptional activity were decreased by 35%, 32%, 56%, and 34%, respectively, in rats with chronic bile fistula. In rats with intact enterohepatic circulation, lovastatin administration resulted in a similar decrease (34%) of cholesterol 7alpha-hydroxylase specific activity. In the second group of experiments, rats with intact enterohepatic circulation were administered a 180 mum bolus of mevalonate followed by a continuous infusion of 180 mumol/h for 1.5, 3, 4.5, and 24 h prior to being killed. Continuous infusion of mevalonate increased cholesterol 7-alpha-hydroxylase specific activity, mRNA levels, and transcriptional activity by an average of 2- to 3-fold at all time intervals. We conclude that under circumstances in which cholesterol is present in excess, cholesterol 7alpha-hydroxylase transcriptional activity is up-regulated and removal of cholesterol from the hepatocytes is facilitated by an increase of bile acid synthesis. When cholesterol availability is decreased, cholesterol 7alpha-hydroxylase transcriptional activity is down-regulated leading to a decreased elimination of cholesterol via bile acid synthesis. In both instances, hepatic cholesterol homeostasis is effectively maintained.
Identifier
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n/a
Format
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Journal Article or Conference Abstract Publication
1993
bile fistula
bile-acid synthesis
Biochemistry & Molecular Biology
biosynthesis
Chiang J Y L
Cloning
enterohepatic circulation
enzyme
hepatic cholesterol
hepatocytes
Heuman D M
HMG-CoA reductase
Hylemon P B
Jones M P
Journal Article or Conference Abstract Publication
Journal of lipid research
liver microsomes
lovastatin
messenger-rna
mevalonate
Pandak W M
Stimulation
Vlahcevic Z R
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
n/a
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
2483-2491
Issue
12
Volume
38
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
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Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Hormonal regulation of cholesterol 7 alpha-hydroxylase specific activity, mRNA levels, and transcriptional activity in vivo in the rat
Publisher
An entity responsible for making the resource available
Journal of Lipid Research
Date
A point or period of time associated with an event in the lifecycle of the resource
1997
1997-12
Subject
The topic of the resource
bile-acid biosynthesis; Biochemistry & Molecular Biology; cholesterol; cholesterol 7 alpha-hydroxylase; cultures; gene; gene cyp7; glucocorticoid; hepatic cholesterol; hepatocyte cultures; liver; messenger-rna levels; monolayer-cultures; primary; protein-kinase-c; regulation; sterol 27-hydroxylase; thyroid; thyroid-hormone
Creator
An entity primarily responsible for making the resource
Pandak W M; Heuman D M; Redford K; Stravitz R T; Chiang J Y L; Hylemon P B; Vlahcevic Z R
Description
An account of the resource
In primary cultures of rat hepatocytes, transcription of the cholesterol 7 alpha-hydroxylase gene is induced synergistically by glucocorticoid and thyroid hormones. The objective of the present study was to evaluate the role of glucocorticoid and thyroid hormones in the maintenance of cholesterol 7 alpha-hydroxylase gene expression in vivo. Male Sprague-Dawley rats underwent adrenalectomy (A), thyroidectomy (T), adrenalectomy + thyroidectomy (A + T), hypophysectomy (H), or sham surgery (paired controls). Ten days post surgery, livers were harvested and cholesterol 7 alpha-hydroxylase specific activity, steady-state mRNA levels, and transcriptional activity were determined. Serum corticosterone levels were <2% of paired controls in A, A + T and H rats. Free thyroxine index was <32% of paired controls in rats with T and H. When compared to sham-operated controls, A + T and H led to decreases in cholesterol 7 alpha-hydroxylase specific activities of 44 +/- 8% and 57 +/- 3%, respectively (P < 0.03 and < 0.05). Similar changes were observed in cholesterol 7 alpha-hyroxylase steady-state mRNA levels, which decreased by 43 +/- 10% (P < 0.001) and 56 +/- 19% (P < 0.05), respectively. Cholesterol 7 alpha-hydroxylase transcriptional activity in A + T and H rats decreased by 34 +/- 11% (P < 0.01) and 61 +/- 4% (P < 0.001), respectively. The observed decreases were greater after H than after A + T, suggesting the possibility that another pituitary hormone plays a role in regulation of cholesterol 7 alpha-hydroxylase. Thyroidectomy alone led to a decrease in cholesterol 7 alpha-hydroxylase specific activity of 37 +/- 7% (P < 0.05) and a trend toward decreased steady-state mRNA levels (21 +/- 12%; P = ns). Adrenalectomy did not significantly decrease cholesterol 7 alpha-hydroxylase specific activity or mRNA levels. Neither thyroidectomy nor adrenalectomy alone affected transcriptional activity. We conclude that under physiologic circumstances, full expression of the cholesterol 7 alpha-hydroxylase gene requires synergistic action of glucocorticoids and thyroid hormone.
Identifier
An unambiguous reference to the resource within a given context
n/a
Format
The file format, physical medium, or dimensions of the resource
Journal Article
1997
bile-acid biosynthesis
Biochemistry & Molecular Biology
Chiang J Y L
Cholesterol
cholesterol 7 alpha-hydroxylase
cultures
gene
gene cyp7
Glucocorticoid
hepatic cholesterol
hepatocyte cultures
Heuman D M
Hylemon P B
Journal Article
Journal of lipid research
Liver
messenger-rna levels
monolayer-cultures
Pandak W M
primary
protein-kinase-c
Redford K
regulation
sterol 27-hydroxylase
Stravitz R T
thyroid
thyroid-hormone
Vlahcevic Z R