title: Androgen regulates development of the sexually dimorphic gastrin-releasing peptide neuron system in the lumbar spinal cord: evidence from a mouse line lacking androgen receptor in the nervous system.
abstract: Androgens including testosterone, organize the nervous system as well as masculine external and internal genitalia during the perinatal period. Androgen organization involves promotion of masculine body features, usually by acting through androgen receptors (ARs). We have recently demonstrated that the gastrin-releasing peptide (GRP) system in the lumbar spinal cord also mediates spinal centers promoting penile reflexes during male sexual behavior in rats. Testosterone may induce sexual differentiation of this spinal GRP system during development and maintain its activation in adulthood. In the present study, we examined the role of ARs in the nervous system regulating the development of the sexually dimorphic GRP system. For this purpose, we used a conditional mouse line selectively lacking the AR gene in the nervous system. AR floxed males carrying (mutants) or not (controls) the nestin-Cre transgene were castrated in adulthood and supplemented with physiological amounts of testosterone. Loss of AR expression in the nervous system resulted in a significant decrease in the number of GRP neurons compared to control littermates. Consequently, the intensity of GRP axonal projections onto the lower lumbar and upper sacral spinal cord was greater in control males than in mutant males. These results suggest that ARs expressed in the nervous system play a significant role in the development of the GRP system in the male lumbar spinal cord. The AR-deletion mutation may attenuate sexual behavior and activity of mutant males via spinal GRP system-mediated neural mechanisms.
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan. Electronic address: hsakamo@uml.okayama-u.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Saito
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7224, 9 quai St Bernard, 75005 Paris Cedex 05, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U952, 9 quai St Bernard, 75005 Paris Cedex 05, France; Université Pierre et Marie Curie, 75005 Paris Cedex 05, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Marie-Luce
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7224, 9 quai St Bernard, 75005 Paris Cedex 05, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U952, 9 quai St Bernard, 75005 Paris Cedex 05, France; Université Pierre et Marie Curie, 75005 Paris Cedex 05, France.
authors.forename: Kalina
authors.initials: K
authors.lastname: Raskin
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Oti
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Satoh
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7224, 9 quai St Bernard, 75005 Paris Cedex 05, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U952, 9 quai St Bernard, 75005 Paris Cedex 05, France; Université Pierre et Marie Curie, 75005 Paris Cedex 05, France.
authors.forename: Sakina
authors.initials: S
authors.lastname: Mhaouty-Kodja
mesh_terms: D000818:Animals; D002369:Castration; D002452:Cell Count; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D008161:Lumbosacral Region; D008297:Male; D008817:Mice, Mutant Strains; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone; D019886:Gastrin-Releasing Peptide
keywords: Androgen receptor; Gastrin-releasing peptide; Mutant mouse; Sexual behavior; Spinal cord; Testosterone