Date of Award:
5-1990
Document Type:
Thesis
Degree Name:
Master of Science (MS)
Department:
Animal, Dairy, and Veterinary Sciences
Committee Chair(s)
Stanley D. Allen
Committee
Stanley D. Allen
Committee
Roger Coulombe
Committee
Mike Hule
Committee
Warren Foote
Committee
Raj Jauhar
Committee
Art Mahoney
Abstract
Ketoconazole is a broad-spectrum antifungal with oral activity and is documented to block steroid biosynthesis in fungi and mammals.
Estradiol-primed ovariectomized rats lose the estradiol-induced, cornified layer of the vaginal epithelium as a result of ketoconazole treatment. This effect is not explained by current knowledge of ketoconazole's mechanism of action.
Ketoconazole's effect on estradiol's binding to either receptors in target tissues (target-cell receptors) or serum-estradiol-carrying proteins in the aforementioned rats was investigated.
The uterus is responsive to estradiol treatment, which causes an increase in uterine size and weight. This tissue is a sensitive means of studying the effects of ketoconazole on target-cell estradiol receptors. Tamoxifen, documented to block the effects of estradiol by binding to target-cell estradiol receptors, was used as a control drug. Uterine weight and horn diameter were measured in estradiol-treated, ovariectomized rats after 7 days of oral, twice-a-day, drug treatment.
Ketoconazole had no effect on mean uterine weights and uterine horn diameters at any of the doses tested; however, tamoxifen at a dose of 10 mg/kg caused a significant reduction in uterine weight and horn diameter. Vaginal histopathology showed that ketoconazole and tamoxifen caused decornification.
The percentage of unbound estradiol in the serum was measured in estradiol-treated, ovariectomized rats treated with ketoconazole orally, twice-a-day for 3 days to determine the effects of ketoconazole on the serum binding of estradiol.
The results of vaginal cytology showed that ketoconazole caused normal decornification. In comparison with control animals, the results of the serum percent-unbound estradiol assays showed that ketoconazole caused a dose-related increase in the percent-unbound estradiol in the blood. The dose required to cause a 5 percent increase in serum unbound estradiol was approximately 6 times greater than the minimum dose required to cause decornification.
Ketoconazole's effects on target-cell estradiol receptors and serum estradiol-carrying proteins do not appear to have any relationship to its effects in causing vaginal decornification in this model.
Checksum
e94376811a03f890e85d89993e695144
Recommended Citation
Hall, Leonard L., "Effects of Ketoconazole on Uterine Weight and on Unbound Serum Estradiol Relative to Vaginal Cornification in Rats" (1990). All Graduate Theses and Dissertations, Spring 1920 to Summer 2023. 4074.
https://digitalcommons.usu.edu/etd/4074
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