Regulation of Fas ligand expression by estrogen in normal ovary.
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.


CONCLUSIONS
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.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA. eva.sapi@yale.edu
Eva
E
Sapi
Wendi D
WD
Brown
Sarit
S
Aschkenazi
Chung
C
Lim
Amanda
A
Munoz
Barry M
BM
Kacinski
Thomas
T
Rutherford
Gil
G
Mor
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta; D030762:Estrous Cycle; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D009924:Organ Culture Techniques; D010051:Ovarian Neoplasms; D010053:Ovary / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D047629:Estrogen Receptor beta; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol