title: Lxrα regulates the androgen response in prostate epithelium.
abstract: Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that commonly occurs in older men. We show that liver X receptor (Lxr)-α knockout mice (lxrα(-/-)) develop ventral prostate hypertrophy, correlating with an overaccumulation of secreted proteins in prostatic ducts and an alteration of vesicular trafficking in epithelial cells. In the fluid of the lxrα(-/-) prostates, spermine binding protein is highly accumulated and shows a 3000-fold increase of its mRNA. This overexpression is mediated by androgen hypersensitivity in lxrα(-/-) mice, restricted to the ventral prostate. Generation of chimeric recombinant prostates demonstrates that Lxrα is involved in the establishment of the epithelial-mesenchymal interactions in the mouse prostate. Altogether these results point out the crucial role of Lxrα in the homeostasis of the ventral prostate and suggest lxrα(-/-) mice may be a good model to investigate the molecular mechanisms of benign prostatic hyperplasia.
authors.affiliation: Department of Génétique Reproduction et Développement, Clermont Université, F-63000 Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.forename: Teresa
authors.initials: T
authors.lastname: Esposito
authors.forename: Julie
authors.initials: J
authors.lastname: Dufour
authors.forename: Aurélien
authors.initials: A
authors.lastname: Pommier
authors.forename: Stephane
authors.initials: S
authors.lastname: Fabre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kemeny
authors.forename: Laurent
authors.initials: L
authors.lastname: Guy
authors.forename: Laurent
authors.initials: L
authors.lastname: Morel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D004847:Epithelial Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D006965:Hyperplasia; D000071518:Liver X Receptors; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000728:Androgens; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger