Submitted October 15, 2007
Returned for revision November 30, 2007
Accepted April 7, 2008
Ovary
Anti-Apoptotic Roles of Prostaglandin E2 and F2alpha in Bovine Luteal Steroidogenic Cells
Anom Bowolaksono ,
Ryo Nishimura ,
Takuo Hojo ,
Ryosuke Sakumoto ,
Tomas J. Acosta ,
and
Kiyoshi Okuda *
* To whom correspondence should be addressed. E-mail: kokuda{at}cc.okayama-u.ac.jp.
Abstract
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 LSC obtained at the mid luteal stage (Days 8-12 of the cycle) were treated for 24 h with PGE2 (0.001-1 µM) and PGF2alpha (0.001-1 µM). PGE2 (1 µM) and PGF2alpha (1 µM) 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. PGE2 and PGF2alpha also attenuated mRNA expression of caspase 3 and caspase 8, and 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) 2 (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 LSC.
Key words:
Apoptosis •
Corpus luteum •
Corpus luteum function •
Progesterone •
Prostaglandins
