Introduction: Tight Junctions and Secretory Activation in the Mammary Gland

Abstract

Studies as early as 1915 showed that the concentration ofsodium and chloride in human milk declined rapidly frombirth to about 5 days post-partum (reviewed in [2]). Figure 1shows these composition changes derived from a more recentstudy [1]. In the cow similar observations were made datingback to the 1930s (reviewed in [3]). Following earlierhypotheses, Barry and Rowland attributed these observationsto variable degrees of mixing of extracellular fluid with thesecretion product of the alveolar cells. Linzell and Peakerstudied the changes in milk composition in detail as part oftheir studies on the mechanisms by which the ioniccomposition of milk is maintained in the dairy goat [4]. Inaddition, they utilized fluxes of isotopes from the bloodstream into the udder or visa versa, and were able to showthat the epithelium is impermeable to disaccharides in thelactating animal. In their article reprinted here [5], theseauthors describe similar experiments in pregnant goatsshowing that changes in sodium, chloride, and lactoseparallel the changes in human milk shown in Fig. 1 and thatduring pregnancy the epithelium is permeable to both lactoseand sucrose. They ascribe these findings to a change in thepermeability of the tight junctions at the onset of lactation.Atthesametimeasthesefunctionalexperimentswerebeingcarried out at Babraham, Cambridge, Dorothy Pitelka and hercolleagues at Berkeley were exploring the cell contacts in theluminal epithelium of the mammary gland at various stages ofdevelopment[6]. They showed four varieties of contacts: tight(occludens) junctions, intermediate (adherens) junctions,desmosomes, and gap junctions. The first three were confinedto epithelial layers and serve both to stabilize their structureand to provide a barrier, which may be selective, between theluminal and basolateral fluid compartments. Gap junctionsformed between epithelial cells but also, in the mammarygland, between epithelial and myoepithelial cells. This classicarticle, reprinted here, continues to inform our understandingof the ultrastructure of the mammary epithelium. It provides,in addition to the structure of the specialized junctionalcomplexes in the murine mammary gland, a very beautifuldevelopmental sequence showing changes in ductal andalveolar cells from pregnancy to lactation and the associatedchanges in the structure of the tight junctions, most beautifullyillustrated by freeze fracture images. Pitelka makes theimportant point that both intermediate junctions and desmo-somes are extremely rare in the epithelium of the lactatinggland, although they can be readily observed at earlier stages.Consistent with the findings of Linzell and Peaker [5], shealso shows that the tight junction in the lactating glandconstitutes a permeability barrier which prevents the flux ofsuch electron opaque substances as ruthenium red andhorseradish peroxidase across the epithelium.Since these two landmark studies, there has been relativelylittle work on this fascinating transition from a highly