Endocrine Abstracts

Prostaglandin (PG) E₂ acts through its receptors (EP_1–4) to modulate myometrial contractions and cervical ripening at term gestation. Although uterine PGE₂ biosynthesis is augmented with labour progression (Durn et al. 2008); functional EP_1–4 receptors have yet to be determined. To characterise these receptors in gravid human myometrium, in vitro responses to selective and novel EP agonists were investigated before and after labour-onset.

Lower segment myometrial biopsies were obtained at Caesarean section from consenting term pregnant donors (38–41 weeks), not in labour (n=10) or in spontaneous labour (n=19). The Local Regional Ethics Committees granted approval for this study. To record contractile responses, myometrial strips were mounted under physiological conditions and attached to isometric force transducers. Vehicle and concentration-effect curves [10⁻¹⁰M to 10⁻⁵M] were constructed for PGE₂, EP₂ agonists (butaprost, CP533,536, AH-13205, AGN211330), EP₄ agonists (AGN201734, L-902688) and EP₁/EP₃ agonists (ONO-D1-004, sulprostone). Data were expressed as a percentage of the final contraction induced by hypotonic shock with distilled water and analysed using two-way ANOVA with Bonferroni’s post-hoc test.

Spontaneous myometrial contractions were attenuated with advancing labour (P<0.001). Before labour-onset, PGE₂ and AGN201734 induced a biphasic response, initially suppressing contractions compared to vehicle controls (P<0.05–P<0.01) with some excitation at 10⁻⁵M. As labour progressed, PGE₂ fully inhibited myogenic activity. In all donor tissues, EP₂ agonists reduced contractions in a monophasic concentration-dependent manner (P<0.05–P<0.001), whilst the other EP₄ mimetics and ONO-D1-004 produced no response. Sulprostone evoked moderate stimulation even during late labour (P<0.01).

These results suggest that predominant utero-relaxant EP₂ transcripts facilitate passage of the foetus during the parturition process whilst EP_1/3 receptors regulate muscle tonus. Targeting these receptors may help to improve tocolytic therapies for labour-associated disorders.

Durn, JH et al. Society for Reproduction and Fertility Online 2008 P87.