?Social odors??sometimes called ?pheromones??are key regulators of infant feeding, reproduction, and aggression. Once detected by the sense of smell, these signals act to modulate the animal's hormonal status. Conversely, steroid metabolites in urine have emerged as one of the best-understood classes of cues detected by the vomeronasal organ, one of the principal sensory organs for pheromones. This tight integration between hormones and olfaction is believed to serve as an ?honest signal? in which information about physiological status is inferred from metabolites of the hormones that control it. In mammals, the identity of most pheromones remains mysterious. In mice, despite 40 years of investigation, the principal sex-specific vomeronasal cues in natural stimuli like urine were controversial or unknown. Recently, my laboratory developed new techniques to perform large scale unbiased screens for the ligands that activate vomeronasal sensory neurons. Using these tools and combining them with neurophysiology, endocrine manipulations, and analysis of behavior, we have identified the first female sex pheromones for the mouse. With support from the NIH, we propose to identify most or all of the male-specific urinary cues that activate the vomeronasal organ. Specifically, we propose to (1) purify male-specific ligands; (2) solve their chemical structures, and (3) identify their pattern of expression and contributions to two behaviors, the Vandenbergh Effect (puberty acceleration) and the Bruce Effect (pregnancy block).
These aims promise to open new doors in our understanding of the relationship between sex, olfaction, hormones, and behavior.
Hormones are powerful regulators of health, mood, and behavior, yet much remains unknown about how sensations and experiences regulate hormones. Mice, through their sense of smell, provide a tractable model for studying how sensory perception regulates behavior and hormonal status, and may provide new insights into the sensory regulation of the timing of puberty and miscarriage. We propose to identify the core stimuli and neuronal mechanisms by which the sense of smell influences hormones and behavior.
