Physiological and pharmacological evaluation of oxytocin-induced milk ejection in mice

Oxytocin, a posterior pituitary hormone, causes the contraction of the mammary myoepithelial cells that surround the acini. This ejects milk from the acini into the primary mammary ducts. The milk ejection responses by oxytocin have not yet been exactly evaluated in mice. Thus, we present a novel method for quantitatively evaluating oxytocin-induced milk ejection in anesthetized lactating mice. We cannulated the mammary duct, administered oxytocin intraperitoneally or intravenously, and collected and measured the ejected milk. Intraperitoneal oxytocin administration (150 mU) induced continuous but oscillatory milk ejection. Repeated intravenous administration of 1.5 mU of oxytocin elicited repeated transient milk ejection. The volume of the ejected milk as a proportion of the stored volume just before each ejection (rather than ejection volume itself) was an expedient and reliable parameter representing the potency of ejection. The oxytocin sensitivity of mice at day 18 of lactation was determined from a sigmoidal dose–response curve as ED(50) ≈ 2.69 mU. Based on this dose–response relationship, the specific activity of the oxytocin receptor agonists (Thr(4), Gly(7))-oxytocin and WAY 267464 were estimated as 976 and 6.87 U/mg, respectively. The assay presented here could be useful for physiological and pharmacological investigations of oxytocin-induced milk ejection.