John Vandenbergh - US grants

health science research support; university;

The purpose of the proposed research is to identify the endocrine and neuroendocrine responses to priming pheromones that modify the onset of puberty. In the housemouse and several other species a urinary pheromone from adult males accelerates the onset of puberty in juvenile females and a urinary pheromone from females in a group inhibits the onset of puberty. We know a good deal about the endocrine response to the male stimulus but little about the female inhibitory stimulus. Under natural conditions, puberty inhibition is an important factor regulating reproduction and population dynamics. Thus, it is essential that the basic response mechanism to puberty inhibiting pheromone in the recipient female is understood. The specific experiments proposed will test: (1) whether urine from grouped females causes the same endocrine changes as the presence of a group of females, (2) whether the inhibitory effect is the result of pituitary unresponsiveness to LHRH, (3) whether the steroid hormone positive feedback mechanism is involved, (4) whether male and female pheromonal cues alter neurotransmitter levels in specific brain areas, and (5) whether induction of early or late puberty by pheromones can have lasting influences on endocrine responsiveness during adult cycling.

biomedical equipment resource;

computer system design /evaluation; biomedical equipment resource; biomedical equipment purchase; computer graphics /printing;

Social stimuli can greatly modify reproductive performance in mammals. In this proposal the influence of social stimulation occurring prior to birth and during the preweaning period on later reproductive performance will be examined in the house mouse. Two series of experiments will be conducted. In the first prenatal influences will be examined. The intra- uterine position of the fetus relative to its littermates can affect its later anatomy, physiology and behavior. Female fetuses located between two males in utero are masculinized compared to female fetuses without male neighbors in-utero. A good deal of laboratory work has been done on this phenomenon. We propose to examine whether such intro-uterine position can affect the later success of the individual in a wild population of mice contained on a segment of a highway interchange. A second series of experiments relates to the finding that mother mice consume significant quantities of their pup;'s urine. About 50% of the water in the mother's milk is water recovered from the pups in the litter. Mice show postpartum estrus and if they become pregnant the next litter goes into a diapause condition. The length of diapause is regulated by the duration and intensity of sucking by the pups. There is a close correlation between the sucking stimulus of the pups and the consumption of pup urine by mothers. We propose to test whether pup urine contains a pheromone which prolongs diapause. In addition, we will test whether diapause is shortened by the presence of adult males or their urine or lengthened by the presence of grouped females of their urine. Changes in diapause length will influence the inter-birth interval in rodents and have a significant effect on the rate of population growth.

APPLICANT'S ABSTRACT: This research will test whether a drug of abuse, cocaine, can influence the ability of an animal to respond to a significant environmental stimulus. We and others have shown that female house mice respond to a pheromone in urine of adult males by attaining puberty significantly earlier than control animals. Our preliminary data suggest this pheromonal stimulus can be blocked by the treatment of cocaine. We propose to confirm this finding and explore whether reception of the pheromone by juvenile females can be attenuated by the administration of cocaine and whether the production of the pheromone by the adult male is altered. The reproductive performance of cocaine-treated females and their daughters will be examined to determine if reproductive competence is compromised by cocaine in the mother and her offspring. Results from these experiments may reveal that an animal can be isolated from elements of its social environment by cocaine. If so, this could have a strong effect on the animal's reproductive fitness since the social environment has a powerful influence on reproductive events. By implication, it may also suggest that cocaine may induce a reduction in responsiveness of humans to significant social stimuli. We anticipate that the results of the research proposed here will lead to the preparation of a multi-year research grant proposal.