Oxytocin and milk removal are required for post-partum mammary-gland development

The oxytocin (OT)-neurophysin preprohormone is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OT is cleaved from its precursor, transported from the magnocellular neurons to the posterior pituitary and secreted during labour and upon the suckling stimulus of pups. OT induces the contraction of myoepithelial cells surrounding the mammary alveoli, which leads to the ejection of milk. Mice deficient in OT are unable to nurse their young. Administration of OT enabled OT-deficient dams to nurse. We now show that OT and milk removal are also required for post-partum alveolar proliferation and mammary-gland function. Alveolar density and mammary epithelial-cell differentiation at parturition was similar in wild-type and OT-deficient dams. However, within 12 h after parturition approx. 2% of the alveolar cells in wild-type dams incorporated DNA and proliferated, but virtually no proliferation was detected in OT-deficient dams. Continuous suckling of pups led to the expansion of lobulo-alveolar units in wild-type but not in OT-deficient dams. Despite suckling and the presence of systemic lactogenic hormones, mammary tissue in OT-deficient dams partially involuted. Our studies demonstrate that post-partum alveolar proliferation requires not only systemic lactogenic hormones, such as prolactin, but also the presence of OT in conjunction with continued milk removal.