Document Detail


Liver X Receptor Modulation of Gene Expression Leading to Pro-Luteolytic Effects in Primate Luteal Cells.
MedLine Citation:
PMID:  22156476     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The expression of genes involved in cholesterol efflux increase, while those involved in extracellular cholesterol uptake decrease, during spontaneous functional regression of the primate corpus luteum (CL). This may result from liver x receptor (LXR, official symbols NR1H3 and NR1H2, respectively) alpha and/or beta control of luteal gene transcription as these nuclear receptor superfamily members are key regulators of cellular cholesterol homeostasis. Therefore, studies were conducted to assess endogenous LXR ligands in the primate CL through the luteal phase, and determine the effect of synthetic or natural LXR ligands on cholesterol efflux and uptake in functional primate luteal cells. Using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS), three LXR ligands were identified and quantified in the rhesus macaque CL including 22R-hydroxycholesterol (22ROH), 27-hydroxycholesterol (27OH), and desmosterol. Levels of 22ROH paralleled serum progesterone (P4) concentrations whereas mean levels of 27OH tended to be higher following the loss of P4 synthesis. Desmosterol was present throughout the luteal phase. Functional macaque luteal cells treated with the synthetic LXR agonist T0901317 (T09) or physiologically relevant concentrations of the endogenous luteal ligands 22ROH, 27OH, and desmosterol, had increased expression of various known LXR target genes and greater cholesterol efflux. Additionally, T09 reduced low density lipoprotein receptor (LDLR) protein and extracellular LDL uptake while 27OH decreased LDLR protein, most-likely via a post-translational mechanism. Collectively, these data support the hypothesis that LXR activation causes increased cholesterol efflux and decreased extracellular cholesterol uptake. In theory, these effects could deplete the primate CL of cholesterol needed for steroidogenesis, ultimately contributing to functional regression.
Authors:
Randy L Bogan; Andrea E Debarber; Jon D Hennebold
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-7
Journal Detail:
Title:  Biology of reproduction     Volume:  -     ISSN:  1529-7268     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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