title: Non-neural androgen receptor promotes androphilic odor preference in mice.
abstract: In mice, male-typical preference for female olfactory cues results largely from sexually differentiated testosterone production. It is currently unclear on which cells and tissues testosterone acts to produce male-typical preference for female olfactory cues. To further address the site of androgen action on olfactory preference, we have developed a loxP-based transgenic mouse that overexpresses androgen receptors (AR) only when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a CMV-Cre driver and a Nestin-Cre driver to overexpress AR selectively in neural tissue. We then examined olfactory preference in transgenic and wildtype (Wt) littermates by simultaneously exposing animals to female-soiled, male-soiled and clean bedding. Ubiquitous overexpression of AR in CMV-AR mice increased preference for male bedding, whereas neural-specific AR overexpression in Nestin-AR transgenic mice did not differ from wildtype siblings in olfactory preference. Neural activation of olfactory brain areas in response to female-soiled bedding was also evaluated in these mice by measuring FOS immunoreactivity. This revealed a decrease in neural activity along the accessory olfactory pathway that accompanied the decrease in preference for female odors in CMV-AR males, compared to both Nestin-AR and Wt male siblings. Together, results indicate that androgens act via non-neural AR to mediate olfactory preference and neural responses to olfactory stimuli, and further suggest that AR in non-neural tissues can promote androphilic odor preferences in male mice.In mice, male-typical preference for female olfactory cues results largely from sexually differentiated testosterone production. It is currently unclear on which cells and tissues testosterone acts to produce male-typical preference for female olfactory cues. To further address the site of androgen action on olfactory preference, we have developed a loxP-based transgenic mouse that overexpresses androgen receptors (AR) only when activated by Cre. We used this transgene to overexpress AR globally in all tissues using a CMV-Cre driver and a Nestin-Cre driver to overexpress AR selectively in neural tissue. We then examined olfactory preference in transgenic and wildtype (Wt) littermates by simultaneously exposing animals to female-soiled, male-soiled and clean bedding. Ubiquitous overexpression of AR in CMV-AR mice increased preference for male bedding, whereas neural-specific AR overexpression in Nestin-AR transgenic mice did not differ from wildtype siblings in olfactory preference. Neural activation of olfactory brain areas in response to female-soiled bedding was also evaluated in these mice by measuring FOS immunoreactivity. This revealed a decrease in neural activity along the accessory olfactory pathway that accompanied the decrease in preference for female odors in CMV-AR males, compared to both Nestin-AR and Wt male siblings. Together, results indicate that androgens act via non-neural AR to mediate olfactory preference and neural responses to olfactory stimuli, and further suggest that AR in non-neural tissues can promote androphilic odor preferences in male mice.
authors.affiliation: Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Swift-Gallant
authors.affiliation: Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Neuroscience, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Coome
authors.affiliation: Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Neuroscience, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada; Department of Cells and Systems Biology, University of Toronto, 100 St. George Street, Toronto, ON M5S 3G3, Canada. Electronic address: ashley.monks@utoronto.ca.
authors.forename: D A
authors.initials: DA
authors.lastname: Monks
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D003463:Cues; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009812:Odorants; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology; D012903:Smell; D013268:Stimulation, Chemical; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: C000607144:AR protein, mouse; D000728:Androgens; D011944:Receptors, Androgen; D013739:Testosterone
keywords: Androgen receptor; Androphilia; Olfactory preference; Sexual differentiation; Transgenic mice