title: Identification of the link between the hypothalamo-pituitary axis and the testicular orphan nuclear receptor NR0B2 in adult male mice.
abstract: The small heterodimer partner (SHP, nuclear receptor subfamily 0, group B, member 2; NR0B2) is an atypical nuclear receptor known mainly for its role in bile acid homeostasis in the enterohepatic tract. We previously showed that NR0B2 controls testicular functions such as testosterone synthesis. Moreover, NR0B2 mediates the deleterious testicular effects of estrogenic endocrine disruptors leading to infertility. The endocrine homeostasis is essential for health, because it controls many physiological functions. This is supported by a large number of studies demonstrating that alterations of steroid activity lead to several kinds of diseases such as obesity and infertility. Within the testis, the functions of the Leydig cells are mainly controlled by the hypothalamo-pituitary axis via LH/chorionic gonadotropin (CG). Here, we show that LH/CG represses Nr0b2 expression through the protein kinase A-AMP protein kinase pathway. Moreover, using a transgenic mouse model invalidated for Nr0b2, we point out that NR0B2 mediates the repression of testosterone synthesis and subsequent germ cell apoptosis induced by exposure to anti-GnRH compound. Together, our data demonstrate a new link between hypothalamo-pituitary axis and NR0B2 in testicular androgen metabolism, making NR0B2 a major actor of testicular physiology in case of alteration of LH/CG levels.
authors.affiliation: Inserm Unit 1103 (A.V., E.M., M.B., A.D.H., J.-P.S., S.B., F.C., J.-M.A.L., D.H.V.), Génétique Reproduction et Développement (GReD), Boîte Postale 80026; Clermont Université (A.V., E.M., M.B., A.D.H., J.-P.S., S.B., F.C., J.-M.A.L., D.H.V.), Université Blaise Pascal, GReD; and Centre National de la Recherche Scientifique (A.V., E.M., M.B., A.D.H., J.-P.S., S.B., F.C., J.-M.A.L., D.H.V.), Unité Mixte de recherche 6293, GReD, F-63170 Aubière Cedex, France; Centre de Recherche en Nutrition Humaine d'Auvergne (A.V., E.M., M.B., A.D.H., J.-P.S., S.B., F.C., J.-M.A.L., D.H.V.), F-63000 Clermont-Ferrand Cedex, France; and Institute of Bioengineering (K.S.), Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vega
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Martinot
authors.forename: Marine
authors.initials: M
authors.lastname: Baptissart
authors.forename: Angélique
authors.initials: A
authors.lastname: De Haze
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saru
authors.forename: Silvère
authors.initials: S
authors.lastname: Baron
authors.forename: Françoise
authors.initials: F
authors.lastname: Caira
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Jean-Marc A
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: David H
authors.initials: DH
authors.lastname: Volle
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D006063:Chorionic Gonadotropin; D018160:Receptors, Cytoplasmic and Nuclear; D011966:Receptors, LHRH; C099713:nuclear receptor subfamily 0, group B, member 2; D013739:Testosterone; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases