Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P293

SFEBES2008 Poster Presentations Reproduction (22 abstracts)

Desensitisation of oxytocin receptors with labour-onset in isolated human myometrium

Deborah Fischer 1 , Diane Farrar 2 , Peter O’Donovan 2 , David Woodward 3 & Kay Marshall 1

1University of Bradford, Bradford, West Yorkshire, UK; 2Bradford Royal Infirmary, Bradford, West Yorkshire, UK; 3Allergan Inc., Irvine, California, USA.

Although oxytocin is a potent stimulant of myometrial contractions, its role in parturition is controversial. The aim of the present study was to elucidate the functional mechanisms of oxytocin receptors in isolated human myometrium before and after labour-onset.

Myometrial biopsies were obtained from consenting women (aged 21–34 years) undergoing Caesarean section at term pregnancy, not in labour (n=6), or in early (n=6) or late (n=6) stages of spontaneous labour. Approval was obtained from the Local Regional Ethics Committees. Myometrial strips were attached to isometric force transducers in physiological conditions and after equilibration, myogenic responses to vehicle (saline) or oxytocin [10−12–10−6 M) were measured. To determine calcium (Ca2+) signalling, primary smooth muscle cells were isolated by enzymatic dispersion of late gestational myometrium (passages 2–3; n=4). Myocytes were exposed to oxytocin (10−6 M) for 0, 3, 16 and 24 h in 96-well plates before incubation with the Ca2+ indicator Fluo-4 AM dye (2 μM). Treatments with oxytocin were performed in triplicate and Ca2+ flux was measured using the FLIPR-Tetra. Estimates of maximal effect (Em) and curve mid-point (pEC50) were expressed as means±S.E.M. and analysed using two-way ANOVA with Bonferroni’s post hoc test.

Responsiveness to oxytocin was greatest in samples taken at term (P<0.001) and continued to augment contractions in tissues harvested shortly after labour-onset (P<0.001). With advancing labour, oxytocin caused little effect. In myocytes, oxytocin alone elevated intracellular Ca2+ in a concentration-dependent manner (pEC50 9.1±0.21). Prolonged pre-treatments with oxytocin attenuated oxytocin-induced Ca2+ transients (P<0.001) and by 24 h, the Em was reduced by 95.7 percent (pEC50 3.4±2.10).

The results indicate that oxytocin enhances myometrial contractility at term pregnancy and early parturition. The untimely desensitisation of oxytocin receptors during late labour or prolonged exposure to oxytocin may contribute to contractile dysfunction. This is currently being researched further.

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