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7. The physiology of Oxytocin

OT binds to specific G-protein coupled cell surface receptors (OT-Rs) on target cells to mediate a variety of physiological effects, largely concerned with reproductive function. The classical physiological roles of OT are the regulation of lactation, parturition and reproductive behavior. Recent data from transgenic animals with targeted disruption of the oxytocin gene (and thus lacking OT) have forced a review of this dogma (14).

7.1. Oxytocin and lactation

In the rat, stimulation of vagal sensory afferents in the nipple by the act of suckling triggers reflex synchronized firing of oxytotic magnocellular neurons in the neurohypophysis, and corresponding pulsatile OT release. OT acts on OT-Rs on smooth muscle cells lining the milk ducts of the breast, initiating milk ejection. OT is essential for completion of this milk ejection reflex in rodent. Mice lacking OT fail to transfer milk to their suckling young. This deficit is corrected by injection of OT. In contrast, women lacking posterior pituitary function can breast-feed normally, illustrating that OT is not necessary for lactation in man. Pituitary lactotrophs express OT-R mRNA, and OT released into the hypophyseal portal blood supply from the median eminence can stimulate prolactin release. However, the role of OT in the physiology of prolactin release remains unclear (3).

7.2. Oxytocin and parturition

OT is a uterotonic agent. In many mammals there is both an increase in OT secretion and an increase in uterine responsiveness to OT during parturition (3). These data suggest a key role for the hormone in the initiation and progression of labour. It is believed that falling progesterone concentrations toward the end of pregnancy lead to up-regulation of uterine myometrial OT-Rs, enhanced contractility, and increased sensitivity to circulating OT. Stretching of the 'birth canal' during parturition leads to the stimulation of specific autonomic afferents, reflex firing of oxytotic neurons and OT release. A positive feedback loop is formed, OT stimulating uterine contraction further and enhancing the production of additional local uterotonic mediators such as prostaglandins. The difficulties of analyzing pulsatile release, and the short circulating half-life of the hormone (due to placental cysteine aminopeptidase), have made it difficult to demonstrate increased circulating OT levels in women during labour. Mice lacking OT have normal parturition. Moreover, women with absent posterior pituitary function can have a normal labour. However, the importance of OT in the birth process is highlighted by the effectiveness of OT antagonists in the management of pre-term labour (15).

7.3. Oxytocin and behavior

OT-R expression is widespread in the CNS of many species. There is clear evidence that OT has important influences on reproductive behavior in rat; facilitating both lordosis and the development of maternal behavior patterns (3). However, mice lacking OT exhibit normal sexual and maternal behavior, suggesting behavioral effects may be species-specific.

7.4. Integrated physiology of Oxytocin

The human and mouse data highlighting normal reproductive function in the absence of OT question the physiological role of the hormone. However, there are some important qualifications. The mouse gravid uterus does not express OT-Rs, in contrast to human and rat. It is not surprising therefore that parturition is normal in the OT null-mouse. In contrast to rat, maternal behavior evolves gradually in mouse, and is not acquired rapidly in the post-partum period. Mouse may therefore not be a good model for the uterine and behavioral effects of OT. Secondly, there may be variable, species-specific redundancy in some of the physiological pathways in which OT is involved. The modeling of OT's role in normal (human) physiology using responses found in its absence (in certain rodents) should thus be made with caution.