Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation

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 [C-14] sucrose and FITC-alb umin (fluorescein isothiocyanate-albumin) into the mammary duct to follow t he 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 (S.E.M.) h. That progesterone withdrawal is the trigger for closure was shown by the finding that injection of progesterone within 4 h of ovar iectomy delayed closure and that closure occurred after injection of the pr ogesterone antagonist RU 486 in intact late pregnant mice. Endocrine ablati on studies showed that low to moderate concentrations of corticosterone and either placental lactogen or prolactin are necessary for tight junction cl osure triggered by progesterone withdrawal. Thus the hormonal requirements for tight junction closure are similar to those shown by other investigator s 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.