Closure of the tight junctions of the mammary epithelium has been shown to accompany the onset of copious milk secretion or lactogenesis, stage 2, in both goats and humans. Here we use injection of [ 14 C]sucrose and FITC-albumin (fluorescein isothiocyanate-albumin) into the mammary duct to follow the course of tight junction closure during lactogenesis in mice. To examine the hormonal changes responsible, we ovariectomized day 16 or 17 pregnant mice and found that closure followed ovariectomy with a mean delay of 13·6 1·5 (...) h. That progesterone withdrawal is the trigger for closure was shown by the finding that injection of progesterone within 4 h of ovariectomy delayed closure and that closure occurred after injection of the progesterone antagonist RU 486 in intact late pregnant mice. Endocrine ablation studies showed that low to moderate concentrations of corticosterone and either placental lactogen or prolactin are necessary for tight junction closure triggered by progesterone withdrawal. Thus the hormonal requirements for tight junction closure are similar to those shown by other investigators to promote lactogenesis, stage 2. Further, the tight temporal control of tight junction permeability suggests that ovariectomy of the late pregnant mouse may be a good model for molecular studies of the lactogenic switch.

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Cultures of mammary epithelium on collagen gels can be induced to secrete the normal complement of milk proteins if the gels are released from the culture dish, allowing them to contract. During the contraction the epithelial cells undergo a shape change from flattened to columnar that initiates secretion of milk proteins. These floating cultures are dependent on hormones and offer a valuable model system for the study of milk secretion and its regulation.