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J Neurosci

Title:		Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses
Author(s):		Raskin K; de Gendt K; Duittoz A; Liere P; Verhoeven G; Tronche F; Mhaouty-Kodja S;
Address:		"Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR) 7148, Genetique Moleculaire-Neurophysiologie et Comportement, and Institut de Biologie, College de France, Paris, France"
Journal Title:		J Neurosci
Year:		2009
Volume:		29
Issue:		14
Page Number:		4461 - 4470
DOI:		10.1523/JNEUROSCI.0296-09.2009
ISSN/ISBN:		1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking)
Abstract:		"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-beta-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 ERalpha-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"
Keywords:		"Animals Cerebrum/metabolism/physiology Female Male Mice Mice, Inbred C57BL Mice, Knockout Models, Genetic Nervous System/*metabolism Neurosecretory Systems/metabolism/*physiology Pregnancy Receptors, Androgen/*deficiency/*genetics/metabolism Sexual Behavi;"
Notes:		"MedlineRaskin, Kalina de Gendt, Karel Duittoz, Anne Liere, Philippe Verhoeven, Guido Tronche, Francois Mhaouty-Kodja, Sakina eng Comparative Study Research Support, Non-U.S. Gov't 2009/04/10 J Neurosci. 2009 Apr 8; 29(14):4461-70. doi: 10.1523/JNEUROSCI.0296-09.2009"