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 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.