Transcription Factors Regulated by CAMP in Smooth Muscle of the Myometrium at Human Parturition
Overview
Affiliations
Cyclic adenosine monophosphate (cAMP) contributes to maintenance of a quiescent (relaxed) state in the myometrium (i.e. uterine smooth muscle) during pregnancy, which most commonly has been attributed to activation of protein kinase A (PKA). PKA-mediated phosphorylation of cytosolic contractile apparatus components in myometrial smooth muscle cells (mSMCs) are known to promote relaxation. Additionally, PKA also regulates nuclear transcription factor (TF) activity to control expression of genes important to the labour process; these are mostly involved in actin-myosin interactions, cell-to-cell connectivity and inflammation, all of which influence mSMC transition from a quiescent to a contractile (pro-labour) phenotype. This review focuses on the evidence that cAMP modulates the activity of TFs linked to pro-labour gene expression, predominantly cAMP response element (CRE) binding TFs, nuclear factor κB (NF-κB), activator protein 1 (AP-1) family and progesterone receptors (PRs). This review also considers the more recently described exchange protein directly activated by cAMP (EPAC) that may oppose the pro-quiescent effects of PKA, as well as explores findings from other cell types that have the potential to be of novel relevance to cAMP action on TF function in the myometrium.
Hinton Jr A, Neikirk K, Le H, Harris C, Oliver A, Martin P Aging Adv. 2025; 1(2):154-171.
PMID: 39839811 PMC: 11748122. DOI: 10.4103/agingadv.agingadv-d-24-00012.
Regulation of 20α-Hydroxysteroid Dehydrogenase Expression in Term Pregnant Human Myometrium Ex Vivo.
Paul M, Barreda A, Gregson A, Kahl R, King M, Hussein W Reprod Sci. 2023; 31(1):150-161.
PMID: 37648943 PMC: 10784398. DOI: 10.1007/s43032-023-01333-6.
Yang H, Huebner K, Hampel C, Erlenbach-Wuensch K, Selvamani S, Shukla V BMC Cancer. 2023; 23(1):480.
PMID: 37237279 PMC: 10223906. DOI: 10.1186/s12885-023-10940-0.
cAMP Compartmentalisation in Human Myometrial Cells.
Varley A, Koschinski A, Johnson M, Zaccolo M Cells. 2023; 12(5).
PMID: 36899855 PMC: 10001376. DOI: 10.3390/cells12050718.
Chen L, Luo Y, Chen Y, Wang L, Wang X, Zhang G Front Genet. 2022; 13:812105.
PMID: 35836580 PMC: 9273953. DOI: 10.3389/fgene.2022.812105.