It is proposed to investigate the effect of reproductive hormones on genital infections in studies involving selected agents that cause sexually transmitted diseases (STDs) using the guinea pig as the animal model system. Emphasis will be placed on extending findings in the applicant's laboratory concerning the effect of estradiol on experimental genital infection of female guinea pigs by the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Treatment with estradiol was found to markedly influence the course of infection producing infections of greater intensity that lasted considerably longer than control animals and resulted in ascending infection with endometritis, cystic salpingitis and cystitis. Projects will include determining the effect of varying concentrations of estradiol, role of systemic and local immune response, attempts to produce response by endogenously produced estradiol and effect of estradiol on growth of GPIC in vitro. Other hormones (progesterone, estrone) will be investigated and experiments simulating oral contraceptives using synthetic hormones will be undertaken. For comparative purposes the effect of estradiol on genital tract infection will be examined for two other STD agents, guinea pig cytomegalovirus (GPCMV), a virus and Candida albicans, an extracellular eukaryotic yeast. Evaluation of response to hormone treatment in animals will involve determination of shedding of the agent, by isolation, altered pathogenesis (necropsy and histopathology), immune response (antibody response in serum and genital secretions using indirect immunofluorescence) and hormone levels in plasma (radioimmunoassay).
