Oxysterol nuclear receptor LXRbeta regulates cholesterol homeostasis and contractile function in mouse uterus.
The uterus is an organ where lipid distribution plays a critical role for its function. Here we show that nuclear receptor for oxysterols LXRbeta prevents accumulation of cholesteryl esters in mouse myometrium by controlling expression of genes involved in cholesterol efflux and storage (abca1 and abcg1). Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased in wild-type mice, whereas under basal conditions, lxralpha;beta(-/-) mice exhibited a marked decrease in abcg1 accumulation. This change resulted in a phenotype of cholesteryl ester accumulation. Besides, a defect of contractile activity induced by oxytocin or PGF2alpha was observed in mice lacking LXRbeta. These results imply that LXRbeta provides a safety valve to limit cholesteryl ester levels as a basal protective mechanism in the uterus against cholesterol accumulation and is necessary for a correct induction of contractions.
Mouzat
Kevin
K
UMR CNRS 6547, "LXRs, Oxysterols, and Steroidogenic Tissues," and Research Center for Human Nutrition, 63177 Aubie`re, France.
Prod'Homme
Magali
M
UMR CNRS 6547, "LXRs, Oxysterols, and Steroidogenic Tissues," and Research Center for Human Nutrition, 63177 Aubie`re, France.
Volle
David H
DH
UMR CNRS 6547, "LXRs, Oxysterols, and Steroidogenic Tissues," and Research Center for Human Nutrition, 63177 Aubie`re, France.
Sion
Benoit
B
Laboratoire de Biologie du Développement et de la Reproduction, Université d'Auvergne, 63058 Clermont-Ferrand, France.
Déchelotte
Pierre
P
CHU Clermont-Ferrand, Service d'Anatomie Pathologique, Hôtel Dieu, Boulevard Léon Malfreyt, 63058 Clermont-Ferrand, France, and.
Gauthier
Karine
K
INSERM EMI 0229, 34298 Montpellier, France.
Vanacker
Jean-Marc
JM
INSERM EMI 0229, 34298 Montpellier, France.
Lobaccaro
Jean-Marc A
JA
UMR CNRS 6547, "LXRs, Oxysterols, and Steroidogenic Tissues," and Research Center for Human Nutrition, 63177 Aubie`re, France. Electronic address: j-marc.lobaccaro@univ-bpclermont.fr.
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002788:Cholesterol Esters / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D008074:Lipoproteins / Q000378:metabolism; D000071518:Liver X Receptors; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009215:Myometrium / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000378:metabolism*
C577836:ABCA1 protein, human; C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002788:Cholesterol Esters; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015237:Dinoprost