Anti-apoptotic roles of prostaglandin E2 and F2alpha in bovine luteal steroidogenic cells.
Production of prostaglandins (PGs) and expression of their receptors have been demonstrated in bovine corpus luteum (CL). The aim of the present study was to determine whether PGE2 and PGF2alpha have roles in bovine luteal steroidogenic cell (LSC) apoptosis. Cultured bovine LSCs obtained at the midluteal stage (Days 8-12 of the cycle) were treated for 24 h with PGE2 (0.001-1 microM) and PGF2alpha (0.001-1 microM). Prostaglandin E2 (1 microM) and PGF2alpha (1 microM) significantly stimulated progesterone (P4) production and reduced the levels of cell death in the cells cultured with or without tumor necrosis factor alpha (TNF)/interferon gamma (IFNG), in the presence and absence of FAS ligand (P < 0.05). Furthermore, DNA fragmentation induced by TNF/IFNG was observed to be suppressed by PGE2 and PGF2alpha. Prostaglandin E2 and PGF2alpha also attenuated mRNA expression of caspase 3 and caspase 8, as well as caspase 3 activity (P < 0.05) in TNF/IFNG-treated cells. FAS mRNA and protein expression were decreased only by PGF2alpha (P < 0.05). A specific P4 receptor antagonist (onapristone) attenuated the apoptosis-inhibitory effects of PGE2 and PGF2alpha in the absence of TNF/IFNG (P < 0.05). A PG synthesis inhibitor (indomethacin) reduced cell viability in PGE2- and PGF2alpha-treated cells (P < 0.05). A specific inhibitor of cyclooxygenase (PTGS), PTGS2 (NS-398), also reduced cell viability, whereas an inhibitor of PTGS1 (FR122047) did not affect it. The overall results suggest that PGE2 and PGF2alpha locally play luteoprotective roles in bovine CL by suppressing apoptosis of LSCs.
Bowolaksono
Anom
A
Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
Nishimura
Ryo
R
Hojo
Takuo
T
Sakumoto
Ryosuke
R
Acosta
Tomas J
TJ
Okuda
Kiyoshi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002417:Cattle / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D003341:Luteolysis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D011374:Progesterone; D015237:Dinoprost; D053148:Caspase 3; D053181:Caspase 8; D015232:Dinoprostone