Effect of proteasome pathway on initiation of mouse labor induced by antiprogesterone.
OBJECTIVE
Various kinds of contraction-associated molecules are up-regulated at the initiation of labor. However, expression profiling has revealed that many molecules are also down-regulated. The effect of down-regulation of molecules by protein degradation on parturition is not known.


METHODS
We administered lactacystin, a specific proteasome inhibitor, to mouse preterm birth model induced by antiprogesterone RU486 on day 16.0 post-coitus. NF-kappaB activity, and the levels of transcripts for oxytocin receptor, prostaglandin F(2alpha) receptor (FP), cyclooxygenase-1, -2, and interleukin-1beta in the uterus were examined by electrophoretic mobility shift assay and semi-quantitative reverse transcriptase-polymerase chain reaction, respectively.


RESULTS
Administration of lactacystin significantly prolonged the time until the delivery of the first pup. FP mRNA level was solely elevated by RU486 treatment, and lactacystin significantly suppressed this up-regulation.


CONCLUSIONS
Proteolysis by proteasomes in the uterus regulates the initiation of labor, at least in part, via control of contraction-associated molecules such as FP.
Kimura
Tadashi
T
Division of Obstetrics and Gynecology, Department of Specific Organ Regulation, Osaka University Graduate School of Medicine, Osaka, Japan. tadashi@gyne.med.osaka-u.ac.jp
Nakamura
Hitomi
H
Ogita
Kazuhide
K
Koyama
Shinsuke
S
Tomiie
Mari
M
Yoshida
Susumu
S
Tsutsui
Tateki
T
Shimoya
Koichiro
K
Koyama
Masayasu
M
Murata
Yuji
Y
D000021:Abortifacient Agents, Steroidal; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D015735:Mifepristone; D016328:NF-kappa B / Q000378:metabolism; D036801:Parturition / Q000378:metabolism*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000378:metabolism
D000021:Abortifacient Agents, Steroidal; D007375:Interleukin-1; D008565:Membrane Proteins; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; C067713:lactacystin; D015735:Mifepristone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine