ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P637

Topographical effects of functional prostanoid and oxytocin receptors on mid-cycle contractions in isolated human myometrium

Deborah Fischer1, Peter O’Donovan2, Diane Farrar2, David Woodward3 & Kay Marshall1

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

Dysfunctional prostanoid and oxytocin receptors have been implicated in the development of myometrial hyperactivity, causing dysmenorrhoea and infertility. The aim of the present study was to investigate the topographical differences in functional contractile PG and oxytocin receptors in mid-cycle isolated myometrium.

Longitudinal, full-thickness sections of the anterior uterus were obtained from consenting pre-menopausal donors (aged 39–48 years) undergoing hysterectomy for benign disorders. Approval for this study was obtained from the Local Regional Ethics Committees. Specimens were harvested at the follicular stage of the menstrual cycle (n=14) and myometrial strips were dissected from lower and fundus ends. For contraction recordings, individual strips were mounted in organ baths under physiological conditions and attached to isometric force transducers. Following tissue equilibration, myogenic responses to vehicle (saline), sulprostone (an EP3/1 agonist), PGF, U46619 (10−9 M–10−5 M) (a stable thromboxane mimetic) and oxytocin (10−12 M–10−6 M) were measured. 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.

The amplitude of phasic spontaneous activity was 19.6 percent greater in lower segment tissue compared to the fundus (P<0.001). Similarly, responsiveness to uterotonins was more pronounced towards the cervix with PG-induced myogenic activity enhanced in a concentration-dependent manner compared to time-matched controls (P<0.01–P<0.001). In contrast, oxytocin significantly augmented myometrial activity in lower (pEC50 6.99±0.75; P<0.001) but not fundus tissues (pEC50 8.59±0.80).

The results indicate that functional regionalisation of the human uterus drives the propagation of intrinsic contractile waves from the lower segment towards the fundus. This may direct retrograde sperm transport and facilitate embryo implantation during the periovulatory stage of the menstrual cycle. Contractile receptor dynamics and mechanotransduction pathways are currently being investigated further to improve the development of treatments for aberrant myometrial function.

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