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The human myometrium differentially expresses mTOR signalling components before and during pregnancy: evidence for regulation by progesterone

Abstract:
Emerging studies implicate the signalling of the mammalian target of rapamycin (mTOR) in a number of reproductive functions. To this date, there are no data regarding the expression of mTOR signalling components in the human myometrium during pregnancy. We hypothesized that mTOR-related genes might be differentially expressed in term or preterm labour as well as in labour or non-labour myometria during pregnancy. Using quantitative RT-PCR we demonstrate for first time that there is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area (lower segment). We used an immortalized myometrial cell line (ULTR) as an in vitro model to dissect further mTOR signalling. In ULTR cells DEPTOR and Rictor had a cytoplasmic distribution, whereas mTOR and Raptor were detected in the cytoplasm and the nucleus, indicative of mTORC1 shuttling. Treatment with inflammatory cytokines caused only minor changes in gene expression of these components, whereas progesterone caused significant down-regulation. We performed a non-biased gene expression analysis of ULTR cells using Nimblegen human gene expression microarray (n = 3), and selected genes were validated by quantitative RT-PCR in progesterone treated myometrial cells. Progesterone significantly down-regulated key components of the mTOR pathway. We conclude that the human myometrium differentially expresses mTOR signalling components and they can be regulated by progesterone.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.jsbmb.2013.02.017

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author


Publisher:
Elsevier
Journal:
Journal of Steroid Biochemistry and Molecular Biology More from this journal
Volume:
139
Pages:
166-172
Publication date:
2013-03-26
Acceptance date:
2013-02-24
DOI:
EISSN:
1879-1220
ISSN:
0960-0760


Language:
English
Keywords:
Pubs id:
pubs:406521
UUID:
uuid:1bfe4c2f-f3bc-4744-ad5e-59f292740198
Local pid:
pubs:406521
Source identifiers:
406521
Deposit date:
2016-07-14
ARK identifier:

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