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Expression and deoxyribonucleic acid-binding activity of the nuclear factor κB family in the human myometrium during pregnancy and labor

Lookup NU author(s): Dr Neil Chapman, Emeritus Professor Nick Europe-Finner, Professor Steve RobsonORCiD

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Abstract

In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. The onset of parturition is itself associated with increases in a number of proinflammatory factors, many of which are regulated by the nuclear factor κB (NF-κB) family of transcription factors. The expression and DNA-binding activity of NF-κB in the myometrium during gestation and parturition were examined. Levels of c-Rel, p50, and p105 NF-κB species were dramatically reduced in pregnant myometrium compared with nonpregnant (NP) controls, whereas expression of the RelA subunit remained uniform. Importantly, during labor, expression of all subunits was observed to be significantly reduced in all myometrial samples studied relative to NP levels. Moreover, for RelA, c-Rel, and p50 subunits, there was a gradient of expression between laboring upper (corpus) and lower uterine segment myometrium. No RelB or p52 subunits could be detected. EMSAs identified changes in NF-κB subunit composition in the myometrium during pregnancy and labor, with p50 homodimers predominant in NP tissues being replaced with RelA:p50 heterodimers in pregnant and laboring samples. Significantly, RelA was observed to be phosphorylated at serine-536, implicating the involvement of the phosphatidylinositol-3-kinase/AKT pathway in NF-κB function in the myometrium.


Publication metadata

Author(s): Chapman NR, Europe-Finner GN, Robson SC

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2004

Volume: 89

Issue: 11

Pages: 5683-5693

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2004-0873

DOI: 10.1210/jc.2004-0873

PubMed id: 15531529


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