Progesterone inhibits contraction and increases TREK-1 potassium channel expression in late pregnant rat uterus.

Zongzhi Yin,Xi Wang,Hongyan Li,Yuanyuan Yang,Wenzhu He,Yun Li,Raouf A Khalil,Yunxia Cao,Bing Shen,Dan Li

doi:10.18632/oncotarget.23084

Abstract

ObjectiveThe aim of this study was to investigate the effect and mechanism by which progesterone regulates uterine contraction in late pregnant ratsResultsProgesterone caused concentration-dependent relaxation of uterine strips that was enhanced compared with control nontreated uterine strips. Uterine strips incubated with progesterone showed a significant increase in TREK-1 mRNA expression and protein level. TREK-1 inhibitor L-methionine partly reversed uterine relaxation caused by the progesterone, while TREK-1 activator arachidonic acid did not cause significant change in progesterone-induced relaxation.ConclusionsProgesterone inhibits uterine contraction and induces uterine relaxation in late pregnancy. The progesterone-induced inhibition of uterine contraction appears to partly involve increased potassium channel TREK-1 expression/activity.Materials and MethodsUterus from late-pregnant rats (gestational day 19) was isolated, and uterine strips were prepared for isometric contraction measurement. Oxytocin-induced contraction was compared in uterine strips pretreated with different concentration of progesterone. TREK-1 potassium channel inhibitor L-methionine and TREK-1 agonist arachidonic acid were used to determine whether the changes caused by progesterone involve changes in TREK-1 activity. The mRNA and protein expression of TREK-1 in uterine tissues were measured using qPCR and Western blot.

Highlights

During the course of normal pregnancy, the human uterus expands in volume dramatically due to hypertrophy and distension of uterine smooth muscle, allowing sufficient space and nutrition for the developing fetus [1].In contrast, the uterus is like a sleeping giant during the third trimester
Uterine stretch causes no further effect on progesterone-induced uterine relaxation. We found that both normal pregnancy and prolonged uterine stretch are associated with decreased myometrium contraction [1]
The present study shows that progesterone inhibits contraction in late pregnant rat uterus, and that the contraction inhibition is partly related to increased TREK-1 expression and activity during late pregnancy

Summary

Introduction

During the course of normal pregnancy, the human uterus expands in volume dramatically due to hypertrophy and distension of uterine smooth muscle, allowing sufficient space and nutrition for the developing fetus [1].In contrast, the uterus is like a sleeping giant during the third trimester. During the course of normal pregnancy, the human uterus expands in volume dramatically due to hypertrophy and distension of uterine smooth muscle, allowing sufficient space and nutrition for the developing fetus [1]. Once the uterus is awaken during fullterm, it transforms into an excitable state and becomes one of the strongest muscles in the human body in order to facilitate birth [2, 3]. The mechanisms underlying uterine quiescence during pregnancy and its remarkable www.impactjournals.com/oncotarget transformation and excitability at term remain major unanswered questions for obstetricians [4]. One of the most pivotal players during pregnancy is the steroid hormone progesterone [5]. The mechanisms via which progesterone regulates uterine contraction are not fully understood

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Conclusion