Receptor-mediated uterine effects of oxytocin and vasopressin

Abstract: The neurohypophyseal hormones oxytocin and vasopressin are important in the regulation of uterine contractility. These hormones, as well as prostaglandin F2?, are most forceful myometrial tissue contractors. Vasopressin is probably a causative factor in primary dysmenorrhoea, whereas oxytocin is the major uterine stimulator of labour, both at term and preterm. In a prospective study we investigated the endometrial gene expression of oxytocin, vasopressin and their receptors by real time PCR in dysmenorrheic and healthy women at time of ovulation (I). Furthermore, we analysed hypophyseal and ovarian hormones as well as prostaglandin F2? metabolite concentrations in plasma in different phases of the menstrual cycle in these women (II). In the pregnant uterus we assayed oxytocin, vasopressin peptide and receptor mRNA’s and prostaglandin F and ovarian steroid receptor mRNA (III). Finally, in double blind, placebo-controlled, cross-over trials in dysmenorrheic and healthy women we validated a model for recording effects of oxytocin and vasopressin V1a antagonists (IV, V). Women with dysmenorrhoea showed a lower endometrial oxytocin receptor mRNA expression at ovulation and had higher oxytocin plasma concentrations at menstruation than healthy women. The vasopressin levels were lower at ovulation. The dysmenorrheic women also had higher levels of FSH in menstrual and oestradiol-17? in late follicle phase. In the pregnant uterus, we found lower oxytocin mRNA and higher oxytocin and prostaglandin F2? receptor mRNA expressions in myometrial tissue before onset of labour at term. In the validation studies we established the influence of vasopressin on uterine contractility in dysmenorrheic and healthy women and on experienced pain in dysmenorrhoea. These effects were inhibited by a non-selective oxytocin and vasopressin V1a receptor antagonist. The results suggest an importance of oxytocin and its receptor in primary dysmenorrhoea. In the pregnant uterus at time of parturition oxytocin seems to be involved in a paracrine system. The high reproducibility and accuracy of the model for measuring effects of vasopressin on the uterus makes it usful in clinical development of antagonists.