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The Journal of Neuroscience, April 8, 2009, 29(14):4461-4470; doi:10.1523/JNEUROSCI.0296-09.2009
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Behavioral/Systems/Cognitive
Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses
Kalina Raskin,1,2 Karel de Gendt,3 Anne Duittoz,4 Philippe Liere,5 Guido Verhoeven,3 François Tronche,1,2 andSakina Mhaouty-Kodja1,2 1Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7148, "Génétique Moléculaire-Neurophysiologie et Comportement," and 2Institut de Biologie, Collège de France, 75231 Paris, France, 3Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium, 4CNRS UMR 6175/Institut National de la Recherche Agronomique, 37380 Nouzilly, France, and 5UMR 788–Inserm–Université Paris XI, 94276 Kremlin Bicêtre, France
Correspondence should be addressed to either Sakina Mhaouty-Kodja or François Tronche, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7148, Génétique Moléculaire-Neurophysiologie et Comportement, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France. E-mail: Email: sakina.mhaouty-kodja{at}college-de-france.fr or Email: francois.tronche{at}gmail.com
Testosterone (T) profoundly influences central sexual differentiation and functions. In the brain, T signals either directly through androgen receptor (AR) or indirectly through estrogen receptor (ER) following aromatization into E2 (17-β-estradiol). As T, through AR, also controls peripheral male sexual differentiation, the relative contribution of central AR in T-mediated regulation of behavioral and neuroendocrine responses still remains unclear. To address this question, we generated, by using Cre-loxP technology, mice selectively lacking AR expression in the nervous system. The mutant male urogenital tract was normally developed, and mice were able to produce offspring. Nonetheless, sexual motivation and performance as well as aggressive behaviors were affected. Only a low percentage of males displayed a complete sexual behavior and offensive attacks. The latency to show masculine behaviors was increased and copulation length prolonged. Erectile activity during mating was also altered. These alterations occurred despite increased levels of T and its metabolites, and an unaffected number of ER
-immunoreactive cells. Olfactory preference and neuronal activation, mapped by Fos immunoreactivity, following exposure to estrus female-soiled bedding were also normal. At comparable T levels, greater differences in masculine behaviors were observed between gonadectomized control and mutant males. AR invalidation in the nervous system also disrupted the somatotropic axis since mutant males exhibited growth retardation and decreased serum levels of insulin-like growth factor I. Our findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somatotropic axes. This genetic model offers a unique opportunity in the understanding of AR's role in cerebral functions of T.
Received Jan. 19, 2009; revised Feb. 20, 2009; accepted Feb. 20, 2009.
Correspondence should be addressed to either Sakina Mhaouty-Kodja or François Tronche, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7148, Génétique Moléculaire-Neurophysiologie et Comportement, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France. E-mail: Email: sakina.mhaouty-kodja{at}college-de-france.fr or Email: francois.tronche{at}gmail.com
This article has been cited by other articles:
J. R. Roney, Z. L. Simmons, and A. W. Lukaszewski
Androgen receptor gene sequence and basal cortisol concentrations predict men's hormonal responses to potential mates
Proc R Soc B, September 30, 2009; (2009) rspb.2009.1538v1.
[Abstract] [Full Text] [PDF]
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