Progesterone is a suppressor of apoptosis in bovine luteal cells.
Progesterone is suggested to be a suppressor of apoptosis in bovine luteal cells. Fas antigen (Fas) is a cell surface receptor that triggers apoptosis in sensitive cells. Furthermore, apoptosis is known to be controlled by the bcl-2 gene/protein family and caspases. This study was undertaken to determine whether intraluteal progesterone (P4) is involved in Fas L-mediated luteal cell death in the bovine corpus luteum (CL) in vitro. Moreover, we studied whether an antagonist of P4 influences gene expression of the bcl-2 family and caspase-3 and the activity of caspase-3 in the bovine CL. Luteal cells obtained from the cows in the midluteal phase of the estrous cycle (Days 8-12 of the cycle) were exposed to a specific P4 antagonist (onapristone [OP], 10(-4) M) with or without 100 ng/ml Fas L. Although Fas L alone did not show a cytotoxic effect, treatment of the cells with OP alone or in combination with Fas L resulted in killing of 30% and 45% of the cells, respectively (P <0.05). DNA fragmentation was observed in the cells treated with Fas L in the presence of OP. The inhibition of P4 action by OP increased the expression of Fas mRNA (P <0.01); however, it did not affect bax or bcl-2 mRNA expression (P >0.05). Moreover, OP stimulated expression of caspase-3 mRNA (P <0.01). The overall results indirectly show that intraluteal P4 suppresses apoptosis in bovine luteal cells through the inhibition of Fas and caspase-3 mRNA expression and inhibition of caspase-3 activation.
Laboratory of Reproductive Endocrinology, Department of Animal Science, Faculty of Agriculture, Okayama University, Okayama 700-8530, Japan. kokuda@cc.okayama-u.ac.jp
Kiyoshi
K
Okuda
Anna
A
Korzekwa
Masami
M
Shibaya
Shuko
S
Murakami
Ryo
R
Nishimura
Miki
M
Tsubouchi
Izabela
I
Woclawek-Potocka
Dariusz J
DJ
Skarzynski
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005260:Female; D006067:Gonanes / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008184:Luteal Cells / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology; D005810:Multigene Family; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000235:genetics
D053222:Fas Ligand Protein; D006067:Gonanes; D006727:Hormone Antagonists; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor; D011374:Progesterone; D053148:Caspase 3; D020169:Caspases; C053238:onapristone