Send to

Choose Destination
J Clin Endocrinol Metab. 2014 Feb;99(2):E320-8. doi: 10.1210/jc.2013-2721. Epub 2013 Nov 25.

Negative effects of progesterone receptor isoform-A on human placental activity of the noncanonical NF-κB signaling.

Author information

Department of Obstetrics, Gynecology, and Reproductive Sciences (B.W., N.P., M.R., T.R.), Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901; and Department of Obstetrics, Gynecology, and Women's Health (N.R.), Rutgers New Jersey Medical School, Newark, New Jersey 07101.



Progesterone (P4)contributes to the maintenance of human pregnancy, in part by inhibiting activity of the human pro-labor genes CRH and cyclooxygenase-2 (COX-2). However, the molecular mechanisms underlying the action of P4 remain poorly defined. We have shown that in human placenta, the constitutively activated noncanonical nuclear factor (NF)-κB pathway positively regulates CRH and COX-2, which is further stimulated by glucocorticoid receptor signaling.


We investigated the role of P4 receptor (PR) in the regulation of nuclear activity of v-rel avian reticuloendotheliosis viral oncogene homolog B (RelB)/NF-κB2 and, in turn, expression of placental CRH and COX-2.


We used a variety of techniques including gene silencing, ectopic expression, chromatin immunoprecipitation, Western blot, quantitative RT-PCR, and immunohistochemical staining assays in human placental tissues and primary culture of human cytotrophoblast.


We identified PR isoform-A (PR-A) as the only isoform of PR produced in human placenta. PR-A levels were lower in term placenta than in midterm placenta. Depletion of PR-A by short interfering RNA derepressed inhibition of CRH and COX-2 by P4 and the synthetic progestin 17α-hydroxyprogesterone caproate. Overexpression of PR-A inhibited transcription of CRH and COX-2, which was further downregulated by treatment with P4 or 17α-hydroxyprogesterone caproate. Such an inhibition was mediated by a negative functional interaction of PR-A with the activity of RelB/NF-κB2.


P4 inhibits the pro-labor genes CRH and COX-2 via PR-A repression of the noncanonical NF-κB signaling in human placenta. Characterization of these pathways may identify potential drug targets for prevention of preterm birth.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center