Progesterone Via its Type-A Receptor Promotes Myometrial Gap Junction Coupling

Effective labour contractions require synchronization of myometrial cells through gap junctions (GJs). Clasically, progesterone (P4) is known to inhibit the expression of connexin-43 (Cx43, major component of GJs) and GJ formation in myometrium. Our current study is based on a striking observation that challenges this dogma. We observed conspicuous differences in the intracellular localization of Cx43 protein in PRA versus PRB expressing myocytes. Thus in P4 stimulated PRA cells Cx43 protein forms GJs, whereas in PRB cells the forward trafficking of Cx43 and GJ formation is inhibited even when Cx43 is overexpressed. We found that P4, via PRA/B, differentially regulates Cx43 translation to generate a Cx43-20 K isoform, which facilitates the transport of full length Cx43 to plasma membrane. The P4 mediated regulation of Cx43 trafficking and GJ formation occurs via non-genomic pathway and involves the regulation of mTOR signaling since inhibition of this pathway restored the Cx43 trafficking defect in PRB cells. We propose that PRA is a master regulator of Cx43 expression, GJ formation and myocyte connectivity/synchronization for labour.

• Publication year

  2017

• Venue

  Scientific Reports

• Publication date

  2017-10-17

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41598-017-13488-9PMID 29042599PMCID 5645358
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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