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(474) INCOMPETENCE OF LUTEOLYSIS IN OVARIES OF SAM MOUSE: ABNORMALITY IN FAS LIGAND/FAS-MEDIATED APOPTOSIS SIGNALING MOLECULES IN LUTEAL CELLS. Kiso, Minako1, Manabe, Noboru1, Shimabe, Munetake1, Miyamoto, Hajime1, 1 Unit of Anatomy and Cell Biology, Kyoto, Japan ABSTRACT- SAM-prone strain (SAMP; a mutant strain from AKR mouse) mice show some reproductive abnormalities and have a shorter reproductive life span than SAM-resistant (SAMR) controls. We found that functional regression and progesterone (P4) dissimilation occurs in abnormally accumulated luteal bodies (aaLBs) of SAMP mice, but structural regression of the luteal cells in the aaLBs is inhibited. During the estrous cycle, no differences between the kinetics of 17b-estradiol and P4 in peripheral blood were observed in SAMP and SAMR mice, indicating that there is no difference in female hormonal regulation between the two strains. In the luteal cells of the aaLBs of the SAMP mice, a high level of activity of 20a-hydroxysteroid dehydrogenase (20aHSD; P4 is catabolized by 20aHSD to a physiologically inactive form) was demonstrated. A deficiency of luteal cell apoptosis causes the aaLBs in SAMP ovaries. To reveal whether the abnormality of Fas ligand (FasL)/Fas-mediated apoptosis signal transducing factors exists in the aaLBs of the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase-8 and caspase-3 mRNAs by quantitative reverse transcription-polymerase chain reaction, and in the expression and localization of FasL, Fas and activated caspase-3 proteins by Western blotting and immunohistochemistry, respectively, during the estrous cycle/luteolysis. The present data showed that these mRNAs and proteins were expressed in normal LBs of both SAMP and SAMR ovaries, but not at all or only in trace amounts in the aaLBs of SAMP mice, indicating that structural regression in the luteal cells of the aaLBs of SAMP mice is inhibited by blockage of the expression of these apoptosis-transducing factors. KEY WORDS: Apoptosis, Luteolysis, Fas ligand and Fas, Intracellular signal |
