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Keywords:

  • Antiprogesterone;
  • initiation of parturition;
  • lactacystin;
  • mouse;
  • preterm birth;
  • proteasome

Problem:  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 of study:  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 F2α receptor (FP), cyclooxygenase-1, -2, and interleukin-1β 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.