Steroid-independent regulation of uterine oxytocin receptors

The oxytocin receptor is an important contractile-associated protein, up-regulated at term in the myometrium in many mammalian species. We conducted studies in a novel animal model to challenge the general view that gonadal steroids are a major regulatory factor of uterine oxytocin receptors. Female marsupials have separate uteri and, in monovular species such as the tammar wallaby, the conceptus is present in one uterus whereas the contralateral uterus is empty. A marked increase in myometrial oxytocin receptors occurs only in the gravid uterus. Fetectomy experiments demonstrated that local embryo-derived factors stimulate this gravid uterus-specific increase in oxytocin receptors, and that uterine distension is probably not a key component in this regulatory pathway. Unilateral ovariectomy has no significant effect on uterine oxytocin receptors, emphasizing the impact of the conceptus on oxytocin receptor regulation and the minimal influence of gonadal steroids on parturition in this species. Our data highlight that regulation of uterine oxytocin receptor expression is multifactorial, and does not necessarily rely on gonadal steroids.