Oncotarget

Research Papers:

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

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

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Oncotarget. 2018; 9:651-661. https://doi.org/10.18632/oncotarget.23084

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Abstract

Zongzhi Yin1,3,4, Yun Li1, Wenzhu He1, Dan Li5, Hongyan Li1, Yuanyuan Yang1, Bing Shen6, Xi Wang7, Yunxia Cao2,3,4 and Raouf A. Khalil7

1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

2Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

3Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, China

4Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei, China

5Department of Scientific Research, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

6Department of Physiology, Anhui Medical University, Hefei, China

7Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Correspondence to:

Raouf A. Khalil, email: [email protected]

Yunxia Cao, email: [email protected]

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

Received: June 27, 2017     Accepted: November 20, 2017     Published: December 07, 2017

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.


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