DIFFERENTIAL REGULATION OF COPPER-ZINC SUPEROXIDE-DISMUTASE AND MANGANESE SUPEROXIDE-DISMUTASE IN THE RAT CORPUS-LUTEUM - INDUCTION OF MANGANESE SUPEROXIDE-DISMUTASE MESSENGER-RIBONUCLEIC-ACID BY INFLAMMATORY CYTOKINES

This study was undertaken to investigate the regulation of mitochondri al manganese superoxide dismutase (Mn-SOD) and cytosolic copper-zinc S OD (Cu,Zn-SOD) in the corpus luteum by inflammatory cytokines. We firs t examined the developmental expression of both SOD mRNAs in the rat c orpus luteum throughout pregnancy. SOD mRNA levels were determined by semiquantitative reverse transcription-polymerase chain reaction. Wher eas Cu,Zn-SOD mRNA levels decreased during late pregnancy, Mn-SOD mRNA levels remained elevated. We secondly examined the effects of inflamm atory reaction on luteal SODs. Rats received injections of lipopolysac charide (LPS; 5 mg, i.p.) on Day 15 of pregnancy, and corpora lutea we re removed 2 h later. LPS caused an increase in Mn-SOD mRNA levels in the corpus luteum and a decrease in serum progesterone levels, but nei ther in levels of Cu,Zn-SOD mRNA. To further study the effects of LPS or LPS-induced cytokines, we incubated either whole corpora lutea obta ined on Day 15 of pregnancy or a temperature-sensitive simian virus-40 transformed luteal fell line (CG-CL; derived from large luteal cells of the corpus luteum of pregnant rats) in serum-free medium with LPS, interleukin-1 alpha (IL-1 alpha), IL- beta, IL-6, and tumor necrosis f actor alpha. LPS anal these cytokines induced a remarkable increase in Mn-SOD mRNA levels in both corpora lutea and GG-CL cells but had no e ffect can Cu,Zn-SOD mRNA expression. In conclusion, Cu,Zn-SOD and Mn-S OD mRNAs are differently expressed and regulated in the corpus luteum of pregnancy. Mn-SOD mRNA, but not Cu,Zn-SOD mRNA, is highly induced b y inflammatory cytokines and may play an important role in protecting luteal cells from inflammation-mediated oxidative damage.