Androgen action within the vomeronasal organ contributes to the sexual differentiation of the brain and behaviour

Martin, Yellow H. (2021) Androgen action within the vomeronasal organ contributes to the sexual differentiation of the brain and behaviour. Masters thesis, Memorial University of Newfoundland.

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Abstract

The vomeronasal organ (VNO), situated in the nasal cavity, is responsible for pheromone processing and plays a critical role in mediating socio-sexual behaviors in mice. Testosterone (T) masculinizes and defeminizes the brain and socio-sexual behavior during early development by acting directly on androgen receptors (AR) or indirectly via estrogen receptors (ER), following aromatization to estradiol. In Experiment 1, we asked whether androgens can act via the VNO in early development to affect the display of socio-sexual behaviors in adulthood by administering a microinjection of T locally to the VNO on the day of birth (PND1) in mice. In Experiment 2, we asked whether T acts on AR or ER by injecting the VNO with a vehicle, estradiol or the nonaromatizable androgen, dihydrotestosterone (DHT) on PND1. In Experiment 3, we took a complementary approach and assessed the necessity of androgen action by blocking AR and ER in the VNO with the aromatase inhibitor letrozole and AR antagonist flutamide on PND1. All three experiments utilized a behavioural battery including a buried food test, olfactory preference test, a resident intruder paradigm, and a test of sexual behavior. In Experiment 1, we found that a single microinjection of T on PND1 was sufficient to alter olfactory investigation and increase territorial aggression in males but did not affect female behavior. In Experiment 2, we found that a single microinjection of DHT on PND1 was sufficient to increase male territorial aggression with increases in boxing, biting, and attacking behavior towards males. In Experiment 3, we found that a single microinjection of letrozole on PND1 was sufficient to increase sexual behaviour with males displaying increased thrusts per mount towards a female intruder. FOS analysis, a marker of neural activity, after exposure to opposite sex odors did not yield any differences between groups in the nucleus accumbens, bed nucleus of the stria terminalis or the medial preoptic area. Our findings suggest that androgens may be acting both directly on AR and indirectly through ER in critical periods of development within the VNO to affect adult sociosexual behavior in male mice.

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