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

Oncotarget. 2017 Dec 7;9(1):651-661. doi: 10.18632/oncotarget.23084. eCollection 2018 Jan 2.

Abstract

Objective: The aim of this study was to investigate the effect and mechanism by which progesterone regulates uterine contraction in late pregnant rats.

Results: Progesterone 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.

Conclusions: Progesterone 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 methods: Uterus 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.

Keywords: TREK-1 channel; pregnancy; progesterone; uterine contraction.