Imperial College London
Alternate

Dr Kaiyu Lei

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 2137k.lei08

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Yulia:2016:10.1210/en.2016-1514,
author = {Yulia, A and Singh, N and Lei, K and Sooranna, SR and Johnson, MR},
doi = {10.1210/en.2016-1514},
journal = {Endocrinology},
pages = {4411--4422},
title = {Cyclic AMP effectors regulate myometrial oxytocin receptor expression},
url = {http://dx.doi.org/10.1210/en.2016-1514},
volume = {157},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The factors that initiate human labor are poorly understood. We have tested the hypothesis that a decline in cAMP/protein kinase A (PKA) function leads to the onset of labor. Initially, we identified myometrial cAMP/PKA-responsive genes (six up-regulated and five down-regulated genes) and assessed their expression in myometrial samples taken from different stages of pregnancy and labor. We found that the oxytocin receptor (OTR) was one of the cAMP-repressed genes, and, given the importance of OTR in the labor process, we studied the mechanisms involved in greater detail using small interfering RNA, chemical agonists, and antagonists of the cAMP effectors. We found that cAMP-repressed genes, including OTR, increased with the onset of labor. Our in vitro studies showed that cAMP acting via PKA reduced OTR expression but that in the absence of PKA, cAMP acts via exchange protein activated by cAMP (EPAC) to increase OTR expression. In early labor myometrial samples, PKA levels and activity declined and Epac1 levels increased, perhaps accounting for the increase in myometrial OTR mRNA and protein levels at this time. In vitro exposure of myometrial cells to stretch and IL-1β increased OTR levels and reduced basal and forskolin-stimulated cAMP and PKA activity, as judged by phospho-cAMP response element-binding protein levels, but neither stretch nor IL-1β had any effect on PKA or EPAC1 levels. In summary, there is a reduction in the activity of the cAMP/PKA pathway with the onset of human labor potentially playing a critical role in regulating OTR expression and the transition from myometrial quiescence to activation.
AU  - Yulia,A
AU  - Singh,N
AU  - Lei,K
AU  - Sooranna,SR
AU  - Johnson,MR
DO  - 10.1210/en.2016-1514
EP  - 4422
PY  - 2016///
SN  - 1945-7170
SP  - 4411
TI  - Cyclic AMP effectors regulate myometrial oxytocin receptor expression
T2  - Endocrinology
UR  - http://dx.doi.org/10.1210/en.2016-1514
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000386774400033&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/43008
VL  - 157
ER  -
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