Prostaglandin F2alpha-induced functional regression of the corpus luteum and apoptosis in rodents.
We investigated the relationship between prostaglandin (PG) F(2)(alpha)-induced functional luteal regression and apoptosis in the rodent ovary. Administration of PGF(2)(alpha) significantly decreased the serum levels of progesterone within 12 h after treatment in pseudopregnant mice. Apparent signals were detected in luteal tissues at 24 to 72 h by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick endo labeling (TUNEL) assay. PGF(2)(alpha) significantly increased the levels of the cleavage nuclear poly (ADP-ribose) polymerase fragment and transforming growth factor-beta (TGF-beta) mRNA within 48 h. PGF(2)(alpha) (10 microM) decreased progesterone secretion 6 to 72 h after its addition in luteinized ovarian cells, whereas C2-ceramide (25 microM) decreased progesterone levels by 44% 72 h after its addition. DNA fragmentation was not observed in the cultured cells treated with PGF(2)(alpha) for 24 h, although cells incubated with C2-ceramide showed fragmentation. Treatment with PGF(2)(alpha) for 1 h caused a distinct decrease in luteinizing hormone (LH)-induced cyclic AMP production. Thus, the inhibitory effect of PGF(2)(alpha) on progesterone secretion may be caused by both the blockage of the functional LH receptor and the activation of apoptotic signaling.
Wang
Zhiyan
Z
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Tamura
Kazuhiro
K
Yoshie
Mikihiro
M
Tamura
Hiroshi
H
Imakawa
Kazuhiko
K
Kogo
Hiroshi
H
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D053938:DNA Fragmentation; D015237:Dinoprost / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood; D011555:Pseudopregnancy / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011374:Progesterone; D015237:Dinoprost; D000242:Cyclic AMP