Down-regulation of the mitogen-activated protein kinase cascade immediately before parturition in the rat myometrium

OBJECTIVE: This study tested the hypothesis that mitogen-activated protein kinase (MAPK) pathway is up-regulated during the course of pregnancy concomitant with uterine hypertrophy. METHODS: The expression and intracellular distribution of components of the MAPK cascade and the activation of MAPKs erk1 and erk2 were examined in the pregnant rat myometrium (day 10-22 of gestation). Protein expression was detected by Western analysis of myometrial subcellular fractions. Mitogen-activated protein kinase activation was studied by detection of tyrosine phosphorylation of erk1 and erk2 kinases and enzymatic activity. RESULTS: Mitogen-activated protein kinase activity increased from day 15 to day 20 of pregnancy. Immediately before parturition, MAPK activity, but not expression, declined sharply. During the same interval, membrane expression of the mitogenic-switching protein ras and the ras activator sos declined. CONCLUSION: The shift in intracellular distribution ras and ras chaperone proteins may precede the down-regulation of membrane-dependent mitogenic signaling and uterine hypertrophy as pregnancy approaches parturition.