Desensitization of oxytocin receptors in human myometrium

Sylvain Phaneuf*, Gergely Asbóth, María P. Carrasco, Belén Rodríguez Liñares, Tadashi Kimura, Ann Harris, Andrés López Bernal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

In the present study, we investigated the possible mechanisms by which oxytocin might regulate oxytocin receptor (OTR) density. Exposure of cultured myometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 103 binding sites/cell, but this was time-dependently reduced to 20.1 x 103 sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR desensitization.

Original languageEnglish (US)
Pages (from-to)625-633
Number of pages9
JournalHuman Reproduction Update
Volume4
Issue number5
DOIs
StatePublished - Sep 1998

Keywords

  • Desensitization
  • Labour
  • Messenger RNA
  • Myometrium
  • Oxytocin receptor

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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