Review Emerging roles for LXRs and LRH-1 in female reproduction Kevin Mouzat a,⇑ , Silvère Baron b,c,d,e , Geoffroy Marceau f , Françoise Caira b,c,d,e , Vincent Sapin f , David H. Volle b,c,d,e , Serge Lumbroso a , Jean-Marc Lobaccaro b,c,d,e,⇑ a Laboratoire de Biochimie, Centre Hospitalier Universitaire de Nîmes, Hôpital Carémeau, Place du Pr. Robert Debré, F-30029 Nimes, France b Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement, BP 10448, F-63000 Clermont-Ferrand, France c CNRS, UMR 6293, GReD, F-63171 Aubiere, France d INSERM, UMR 1103, GReD, F-63171 Aubiere, France e Centre de Recherche en Nutrition Humaine d’Auvergne, F-63000 Clermont-Ferrand, France f Laboratoire de Biochimie Médicale, Faculté de Médecine, Université d’Auvergne, Place Henri Dunant, F63000 Clermont-Ferrand, France article info Article history: Available online xxxx Keywords: Female reproduction Cholesterol controlling nuclear receptors LXR LRH1 abstract Nutritional status is known to control female reproductive physiology. Many reproductive pathologies such as anorexia nervosa, dystocia and preeclampsia, have been linked to body mass index and to meta- bolic syndrome. Lipid metabolism has also been associated with ovarian, uterine and placental functions. Among the regulators of lipid homeostasis, the Liver X Receptors (LXRs) and the Liver Receptor Homolog- 1 (LRH-1), two members of the nuclear receptor superfamily, play a central role. LXRs are sensitive to intracellular cholesterol concentration and decrease plasma cholesterol, allowing to considering them as ‘‘cholesterol sensors’’. LRH-1 shares many target-genes with LXRs and has been considered for a long time as a real orphan nuclear receptor, but recent findings showed that phospholipids are ligands for this nuclear receptor. Acting in concert, LXRs and LRH-1 could thus be sensitive to slight modifications in cel- lular lipid balance, tightly maintaining their cellular concentrations. These last years, the use of trans- genic mice clarified the roles of these nuclear receptors in many physiological functions. This review will be focused on the roles of LXRs and LRH-1 on female reproduction. Their contribution to ovarian endocrine and exocrine functions, as well as uterine and placental physiology will be discussed. The future challenge will thus be to target these nuclear receptors to prevent lipid-associated reproductive diseases in women. Ó 2012 Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction .......................................................................................................... 00 1.1. Lipid metabolism and female reproduction ............................................................................ 00 1.1.1. Ovarian considerations ..................................................................................... 00 1.1.2. In the uterus ............................................................................................. 00 1.1.3. Lipids and placental function................................................................................ 00 2. Liver X Receptors (LXRs), two hypocholesterolemiant factors .................................................................. 00 2.1. Structure of the LXRs ............................................................................................. 00 2.2. Transcriptional activity of the LXRs .................................................................................. 00 2.3. LXRs, two nuclear receptors activated by cholesterol derived molecules, and blocked by PUFAs ................................. 00 2.4. Role of LXRs in female reproduction ................................................................................. 00 2.4.1. LXRs and ovarian function .................................................................................. 00 2.4.2. LXRs and uterus .......................................................................................... 00 2.4.3. Physiologic roles of LXRs in placenta ......................................................................... 00 3. Liver Receptor Homolog-1 (LRH-1), a phospholipid-bound nuclear receptor....................................................... 00 3.1. Structure and mechanism of action .................................................................................. 00 0303-7207/$ - see front matter Ó 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.mce.2012.06.009 ⇑ Corresponding authors. Address: ‘‘Génétique Reproduction et Développement’’, Unité Mixte de Recherche, CNRS 6293, Clermont Université, INSERM U1103, 24 Avenue des Landais, BP 80026, 63171 Aubière Cedex, France (J.-M. Lobaccaro). E-mail addresses: kevin.mouzat@chu-nimes.fr (K. Mouzat), j-marc.lobaccaro@univ-bpclermont.fr (J.-M. Lobaccaro). Molecular and Cellular Endocrinology xxx (2012) xxx–xxx Contents lists available at SciVerse ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce Please cite this article in press as: Mouzat, K., et al. Emerging roles for LXRs and LRH-1 in female reproduction. Molecular and Cellular Endocrinology (2012), http://dx.doi.org/10.1016/j.mce.2012.06.009