title: Nonneural Androgen Receptors Affect Sexual Differentiation of Brain and Behavior.
abstract: Testosterone, acting via estrogenic and androgenic pathways, is the major endocrine mechanism promoting sexual differentiation of the mammalian nervous system and behavior, but we have an incomplete knowledge of which cells and tissues mediate these effects. To distinguish between neural and nonneural actions of androgens in sexual differentiation of brain and behavior, we generated a loxP-based transgenic mouse, which overexpresses androgen receptors (ARs) when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a cytomegalovirus (CMV)-Cre driver (CMV-AR), and we used a Nestin-Cre driver to overexpress AR only in neural tissue (Nes-AR). We then examined whether neural or global AR overexpression can affect socio-sexual behaviors using a resident-intruder paradigm. We found that both neural and global AR overexpression resulted in decreased aggressive behaviors and increased thrusting during mounting of intruders, consistent with a neural site of action. Global, but not neural, AR overexpression in males led to an increase in same-sex anogenital investigation. Together, these results suggest novel roles for nonneural AR in sexual differentiation of mice, and indicate that excess AR can lead to a paradoxical reduction of male-typical behavior.
authors.affiliation: Departments of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), Neuroscience (L.A.C., F.R., D.A.M.), and Cells and Systems Biology (D.A.M.), University of Toronto, Toronto, Ontario, Canada M5S 3G3; and Department of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), University of Toronto, Mississauga, Mississauga, Ontario, Canada L5L 1C6.
authors.forename: Ashlyn
authors.initials: A
authors.lastname: Swift-Gallant
authors.affiliation: Departments of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), Neuroscience (L.A.C., F.R., D.A.M.), and Cells and Systems Biology (D.A.M.), University of Toronto, Toronto, Ontario, Canada M5S 3G3; and Department of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), University of Toronto, Mississauga, Mississauga, Ontario, Canada L5L 1C6.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Coome
authors.affiliation: Departments of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), Neuroscience (L.A.C., F.R., D.A.M.), and Cells and Systems Biology (D.A.M.), University of Toronto, Toronto, Ontario, Canada M5S 3G3; and Department of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), University of Toronto, Mississauga, Mississauga, Ontario, Canada L5L 1C6.
authors.forename: Firyal
authors.initials: F
authors.lastname: Ramzan
authors.affiliation: Departments of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), Neuroscience (L.A.C., F.R., D.A.M.), and Cells and Systems Biology (D.A.M.), University of Toronto, Toronto, Ontario, Canada M5S 3G3; and Department of Psychology (A.S.-G., L.A.C., F.R., D.A.M.), University of Toronto, Mississauga, Mississauga, Ontario, Canada L5L 1C6.
authors.forename: D Ashley
authors.initials: DA
authors.lastname: Monks
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects* / Q000254:growth & development; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics*; D012733:Sex Differentiation / Q000235:genetics*; D012726:Sexual Behavior, Animal; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D013739:Testosterone