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Oxytocin signalling in human myometrium
S Phaneuf1, G N Europe-Finner, M P Carrasco
1Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, England.
Advances in Experimental Medicine and Biology
|January 1, 1995
Summary
Oxytocin stimulates uterine contractions via G-proteins and phospholipase C in human myometrial cells. Oestradiol upregulates this response, while protein kinase C inhibits it, revealing key mechanisms in labour.
Area of Science:
- Reproductive Biology
- Cellular Signaling
- Endocrinology
Background:
- Oxytocin's role in uterine contractions is established but its precise molecular mechanisms require definition.
- Oxytocin signaling involves phospholipase C activation, inositol trisphosphate production, and intracellular calcium release, with suspected G-protein involvement.
Purpose of the Study:
- To elucidate the signaling mechanisms of oxytocin action in human myometrial cells.
- To identify the specific G-proteins and phospholipase C isoforms mediating the oxytocin response.
- To investigate the modulatory effects of oestradiol and protein kinase C on oxytocin signaling.
Main Methods:
- Measurement of inositol phosphate formation and intracellular calcium concentration changes in cultured human myometrial cells.
- Utilized pertussis toxin to differentiate G-protein involvement (Gq vs. Gi).
- Employed Western blotting to detect G-protein and phospholipase C isoform expression.
Main Results:
- Oxytocin dose-dependently stimulated inositol phosphate formation and intracellular calcium release.
- Both pertussis toxin-sensitive (Gi) and -resistant (Gq) G-proteins mediate the oxytocin response.
- Specific G-protein alpha subunits (q, 11, 2, i1, i2, i3) and phospholipase C beta isoforms (1, 2, 3) were identified.
- Protein kinase C activation inhibited oxytocin signaling, while its inhibition potentiated the response.
- Oestradiol upregulated oxytocin responsiveness via a post-receptor mechanism, reversible by tamoxifen.
Conclusions:
- Oxytocin activates human myometrial cells through distinct Gq and Gi protein pathways, leading to calcium mobilization.
- Protein kinase C exerts negative feedback on oxytocin signaling, and oestradiol enhances oxytocin responsiveness.
- These findings provide a detailed molecular understanding of oxytocin's action in the myometrium, relevant to labor physiology.