LXR FXR
RXR and its Brothers

Author: Gianpiero Pescarmona
Date: 17/07/2011

Description

DEFINITION

A short protein description with the molecular wheight, isoforms, etc...
Use, when available, the link to Wikipedia (Es Trypsin)

THE GENE

DatabaseLXRaLXRbFXR
WikigenesNR1H3NR1H2NR1H4
GeneCards"NR1H3":"NR1H2":"NR1H4":
Your Favorite Gene Sigma"NR1H3":"NR1H2":"NR1H4":

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage

LuXuRies of Lipid Homeostasis: The Unity of Nuclear Hormone Receptors, Transcription Regulation, and Cholesterol Sensing, 2002

SYNTHESIS AND TURNOVER

mRNA synthesis

FXR

statin

&so_a=&so_j=

protein synthesis

post-translational modifications
degradation

CELLULAR FUNCTIONS

cellular localization,
biological function

Cholesterol Sensing

DatabaseLink
KEGG PathwaysPPAR pathwayBile Secretion
  • Cell signaling and Ligand transport

REGULATION

serum cholesterol glucocorticoid

serum cholesterol glucocorticoids

Biochim Biophys Acta. 1978 Jun 23;529(3):409-18.
Circadian rhythm of cholesterol-7alpha-hydroxylase and cortisol in the African green monkey (Cercopithecus aethiops). 1978
Hulcher FH, Margolis RD, Bowman DJ.
Abstract

Cholesterol-7alpha-hydroxylase in African green monkey liver had an apparent Km of 1.65-10(-4) M cholesterol and a pH optimum of 7.4. The amplitudes of the circadian maxima of enzyme activity and serum cortisol levels were significantly greater in vervets than in grivets. Fluctuations in enzyme activity and cortisol levels during the circadian cycle were positively correlated (r = 0.89). Enzyme activities and hormone levels were 2.7-fold lower over a 24-h period in the grivet than in the vervet. Cholesterol feeding reduced the enzyme activity by 40% and serum cortisol was reduced to 38% of control levels at the diurnal peak. Serum glucocorticoids may be important physiological regulators of cholesterol-7alpha-hydroxylase in non-human primates. The concentration of cortisol and its time of release appear to be factors in the hyperresponsive trait of grivets. Genetic differences between vervet and grivet races may account for differences in the amplitude and timing of the circadian rhythm of cholesterol-7alpha-hydroxylase activity possibly influenced by cortisol.

Biochem Int. 1985 Feb;10(2):177-85.
Circadian rhythm of HMG-CoA reductase and insulin in African green monkeys. 1985
Hulcher FH, Reynolds J, Rose JC.
Abstract

HMG-CoA reductase in hepatic microsomes and serum insulin display circadian rhythm in two strains of Cercopethicus aethiops. Grivets develop higher levels of serum cholesterol than vervets fed cholesterol. Males (n = 20/gp) were adapted to a light cycle (7:30 a.m.-8:30 p.m.) for 60 days and fed a non-cholesterol diet at 8:30 a.m. and 2:00 p.m. Vervet acrophase, reductase activity was synchronized to serum insulin units with a specific activity of 1480 pmol/min/mg protein changing by 7.5-fold from nadir to acrophase. The activity profile in grivets was asynchronous to vervet fluctuations with peaks at 12 noon (160 pmol/min/mg) and 6 p.m. (275 pmol/min/mg). Insulin levels also peaked near these times. The 24-h reductase activity was over 4 times greater in vervet than grivet livers. The similar rhythmic patterns of reductase and insulin support the notion that insulin plays an important role in the rhythm of HMG-CoA reductase in primates.

Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol buffering capacity. 2000 Proc Soc Exp Biol Med. 2000 May;224(1):8-19.
Ness GC, Chambers CM.
Source

Regulation of the expression of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by the major end product of the biosynthetic pathway, cholesterol, and by various hormones is critical to maintaining constant serum and tissue cholesterol levels in the face of an ever-changing external environment. The ability to downregulate this enzyme provides a means to buffer the body against the serum cholesterol-raising action of dietary cholesterol. The higher the basal expression of hepatic HMG-CoA reductase, the greater the "cholesterol buffering capacity" and the greater the resistance to dietary cholesterol. This review focuses on the mechanisms of feedback and hormonal regulation of HMG-CoA reductase in intact animals rather than in cultured cells and presents the evidence that leads to the proposal that regulation of hepatic HMG-CoA reductase acts as a cholesterol buffer. Recent studies with animals have shown that feedback regulation of hepatic HMG-CoA reductase occurs at the level of translation in addition to transcription. The translational efficiency of HMG-CoA reductase mRNA is diminished through the action of dietary cholesterol. Oxylanosterols appear to be involved in this translational regulation. Feedback regulation by dietary cholesterol does not appear to involve changes in the state of phosphorylation of hepatic HMG-CoA reductase or in the rate of degradation of this enzyme.
Several hormones act to alter the expression of hepatic HMG-CoA reductase in animals. These include insulin, glucagon, glucocorticoids, thyroid hormone and estrogen.

  • Insulin stimulates HMG-CoA reductase activity likely by increasing the rate of transcription, whereas glucagon acts by opposing this effect. Hepatic HMG-CoA reductase activity undergoes a significant diurnal variation due to changes in the level of immunoreactive protein primarily mediated by changes in insulin and glucagon levels.
  • Thyroid hormone increases hepatic HMG-CoA reductase levels by acting to increase both transcription and stability of the mRNA.
  • Glucocorticoids act to decrease hepatic HMG-CoA reductase expression by destabilizing reductase mRNA.
  • Estrogen acts to increase hepatic HMG-CoA reductase activity primarily by stabilizing the mRNA.
    Deficiencies in those hormones that act to increase hepatic HMG-CoA reductase gene expression lead to elevations in serum cholesterol levels. High basal expression of hepatic HMG-CoA reductase, whether due to genetic or hormonal factors, appears to result in greater cholesterol buffering capacity and thus increased resistance to dietary cholesterol.

Glucocorticoid use and serum lipid levels in US adults: the Third National Health and Nutrition , 2005 Arthritis Rheum. 2005 Aug 15;53(4):528-35.

OBJECTIVE:

It has been generally perceived that glucocorticoids adversely affect serum lipid levels, although results of prospective studies have suggested the contrary. In this study, we sought to examine the relationship between glucocorticoid use and lipid profiles in a nationally representative sample of subjects.
METHODS:

Using data from 15,004 participants ages 20 years and older in The Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between glucocorticoid use and serum lipid profiles. Glucocorticoid use was determined from the household interview regarding prescription medication use. We used multivariate linear regression to adjust for age, sex, race or ethnicity, education, smoking status, body mass index, physical activity, alcohol consumption, energy fraction from protein and carbohydrates, and total energy intake.
RESULTS:

Glucocorticoid use was associated with a higher serum high-density lipoprotein (HDL) cholesterol level and a lower ratio of total cholesterol-to-HDL cholesterol among subjects ages 60 years or older (multivariate difference 9.0 mg/dl [95% confidence interval (95% CI) 3.9, 14.1] and -0.6 mg/dl [95% CI -0.9, -0.3], respectively) but not among those younger than age 60 years (multivariate difference -1.5 mg/dl [95% CI -5.4, 2.5] and 0.1 mg/dl [95% CI -0.3, 0.5], respectively). Correspondingly, glucocorticoid use was associated with a higher serum apolipoprotein A-I (Apo A-I) level and a lower Apo A-I:Apo B ratio (multivariate difference 12.1 mg/dl [95% CI 2.9, 21.3] and 0.16 mg/dl [95% CI 0.03, 0.29], respectively) only among subjects ages 60 years or older. Inhalation/intranasal glucocorticoid use was also associated with a higher serum HDL cholesterol level (multivariate difference 4.9 mg/dl [95% CI 0.3, 9.5]) only among subjects ages 60 years or older.
CONCLUSION:

Our results suggest that glucocorticoid use is not associated with an adverse lipid profile in the US population and may be associated with a favorable lipid profile among persons ages 60 years or older, in concordance with previous prospective studies.

DIAGNOSTIC USE

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