Protective effect of the selective estrogen receptor modulator LY117018 on rat vaginal Candida albicans colonization.
Although we know that estrogen promotes vaginal colonization with Candida albicans in oophorectomized rats, the availability of selective estrogen receptor modulators (SERMs) raises the question of whether these compounds may influence the susceptibility of vaginal epithelium to Candida colonization. We inoculated rats with viable C. albicans 2 days after treatment with oil vehicle (controls), estradiol cypionate or the proprietary SERM, LY117018. LY117018 prevented colonization by a clinical isolate of C. albicans. In contrast, rats treated with estradiol cypionate remained colonized for up to 10 days after initial inoculation with viable yeast. In vitro tests demonstrated that both estradiol-17beta and LY117018 promoted growth at a 1 x 10(-9) M concentration, whereas both compounds suppressed yeast growth at a higher (1 x 10(-6) M) concentration. The effect of LY117018 on vaginal colonization could not be predicted on the basis of in vitro investigation. We conclude that the protective effect of LY117018 resulted from an indirect effect on the host and not from its effect directly on the microorganism.
Essmann
M
M
Infectious Disease Research Laboratory, University of Osteopathic Medicine and Health Sciences, Des Moines, Iowa, USA.
Larsen
B
B
D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology*; D014621:Vagina / Q000382:microbiology*; D014626:Vaginal Smears
D004965:Estrogen Antagonists; D011759:Pyrrolidines; D013876:Thiophenes; D004958:Estradiol; C025430:LY 117018