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Regulation of Fas Ligand Expression By Estrogen in Normal Ovary

Departments of Therapeutic Radiology and Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut eva.sapi{at}yale.edu

Wendi D. Brown, MD

Sarit Aschkenazi, MD

Chung Lim, MD

Amanda Munoz, BS

Barry M. Kacinski, MD, PhD

Thomas Rutherford, MD, PhD

Gil Mor, MD, PhD

Departments of Therapeutic Radiology and Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.

Objective: The clinical significance of the Fas/Fas ligand (FasL) system in hormone-sensitive carcinomas such as breast and ovary has been reported. However, only a few studies have investigated the potential hormonal regulation of its expression. In this study, we evaluated the expression of FasL in normal ovarian tissue during the normal female reproductive cycle with the goal of identifying potential hormones that can regulate FasL expression.

Methods: We used Western blot analysis to examine the expression of FasL in the rat ovary throughout the natural estrous cycle. We employed Western blot and reverse transcriptase-polymerase chain reaction to study hormonal regulation of FasL in human ovarian epithelial cells and normal ovarian tissues.

Results: FasL protein expression levels change in the ovary during the female reproductive cycle. FasL protein appeared intensively in estrus, declined sharply in metestrous, further decreased to a very low level in diestrus, and was absent in proestrus. Because the protein expression pattern of FasL in the cycling ovary was similar to the estrogen receptor beta expression pattern, we examined the effect of estrogen on the level of FasL protein and found that estrogen indeed upregulates the expression of FasL protein and mRNA levels in ovarian epithelial cells as well as in normal ovarian tissues. Furthermore, we showed that the estrogen-induced increase in the FasL protein and mRNA levels could be abolished by 4-hydroxytamoxifen, which suggests that the observed increase in FasL expression was mediated by estrogen receptor.

Conclusion: Our findings support the hypothesis that the expression of FasL in normal ovary is hormonally sensitive and could have a key role in the physiology of normal ovarian tissue.

Key Words: Reproductive cycle • 4 hydroxytamoxifen • organ culture • ovarian cancer • apoptosis

Journal of the Society for Gynecologic Investigation, Vol. 9, No. 4, 243-250 (2002)
DOI: 10.1177/107155760200900411


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