A Study Of Regulation On Human Pregnant Myometrium Contractile Activity

In this study, we used immune histochemistry to observe the distribution of CRH receptor protein expression in fundus and lower segment of myometriums obtained from term labouring and non-labouring women. We investigated the direct effects of CRH and its related peptide UrocortinII on human pregnant myometrial strips by isometric tension recordings. By adding CRH-R antagonists, the possible route by which CRH exerts its effect was investigated. The capability of synthetic CRH to modulate the activity of prostaglandin F2a and oxytocin, and the tocolytic effects of L-type Ca⁺⁺-channel blocker verapamil, magnesium sulfate, progesterone and nitric oxide donor sodium nitroprusside on human uterine contractility in relation to labour are also investigated. Using immunofluorescence analysis, RT-PCR and Western-blot, we investigated the regulation of CRH on PGHS-2 in the cultured chorion trophoblast cells. Our results showed: 1) CRHR1 and CRHR2 receptor protein were distributed in the cytoplast and cytomembrane of smooth muscle cells in the fundus and lower segment of term labour or non-labour pregnant myometrium.2) CRH inhibited the myometrium contractility in TNL, but in TL the effect of CRH did not occur until reaching a high concentration. CRHR1 antagonist antalamin completely abolished the effect, but CRH-R2 antagonist astressin 2B had no effect. 3) CRH significantly increased the myometrium reaction to PGF2a, but had no effects on oxytocin induced contractility. 4) The inhibitory effect of verapamil was greater in TNL than in TL, MgSO4 showed no different effects in the two groups.5) Progesterone showed an immediate inhibitory effect on strips both in TNL and TL in a dose-dependent manner. The progesterone antagonist RU486 completely abolished the effect of progesterone.6) SNP showed a relative weak inhibitory effect both in TL and TNL groups.7) CRHR1 and CRHR2 receptor protein were positive in the cytoplasma and cell membrane of chorion trophoblast cells. CRH antagonistα-helical CRH 9-41 increased the transcript and protein levels of PGHS-2 in cultured chorion trophoblast cells. Exogenous CRH decreased the expression of mRNA and protein of PGHS-2 in a dose dependent manner.