This research aims to delineate the molecular mechanisms through which sexual pheromones initiate chemosignalling and thereby influence physiology and behavior. The vomeronasal organ (VNO) plays an important role in perception of pheromones, species-specific chemical signals that influence hormone levels, fertility and sexual behavior. The identification of (Z)-77-dodecen-1-yl acetate (Z7-12:Ac) as a female-to-male sex pheromone in Asian elephants now makes it possible to study pheromonal processes in;higher mammals at the levels of molecules, cells, and organisms. This system has the distinct advantages that Z7-12:Ac is a well-characterized sex pheromone in moths and a proven photolabeled analog is available, the quantitative bioassay is robust, the emitter source (preovulatory urine) is abundantly available , and the large size of the VNO receptive tissue will allow unusual molecular studies in both elephant urine and VNO receptor tissue. These proteins will be purified, characterized, and genetically cloned. Throughout the molecular procedures, the continuity of bioactivity will be confirmed by bioassays.
Specific aims are: (1) to demonstrate sustained behavioral responses to the photoaffinity-labeled,tritiated diazoacetate analog of the pheromone (Z7-12:Dza). This step is essential because Z7-12:Dza will be used to identify biologically relevant proteins from estrous urine (EUP) and male elephant vomeronasal organ (EVNOP). (2) to purify EUP and EVNOP using Z7-12:Dza as a marker. After these proteins have been purified and shown to sustain biological activity, preparative purification will be undertaken with continual confirmation of bioactivity. (3) to characterize the pheromone-binding proteins by cytochemical and genetic techniques. Thus, the purified proteins will be subjected to antibody production for immunocytochemistry, and also partial sequencing and identification of the ligand-binding sites for the preparation of mRNAs. This work will lead to the preparation of cDNA libraries for these binding/receptor proteins from female tissues and discrete sensory VO regions. The VNO chemoreceptive system of the elephant has the potential to be an outstanding model system for sensory defects, such as motivation and deprivation and hormonal depletions.
| Lazar, Josef; Rasmussen, L E L; Greenwood, David R et al. (2004) Elephant albumin: a multipurpose pheromone shuttle. Chem Biol 11:1093-100 |
| Lazar, Josef; Greenwood, David R; Rasmussen, L E L et al. (2002) Molecular and functional characterization of an odorant binding protein of the Asian elephant, Elephas maximus: implications for the role of lipocalins in mammalian olfaction. Biochemistry 41:11786-94 |
| Rasmussen, L E (2001) Source and cyclic release pattern of (Z)-7-dodecenyl acetate, the pre-ovulatory pheromone of the female Asian elephant. Chem Senses 26:611-23 |
