Tight Junction Regulation in the Mammary Gland

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Abstract

Tight junctions form a narrow, continuous sealthat surrounds each endothelial and epithelial cell atthe apical border, and act to regulate the movement ofmaterial through the paracellular pathway. In the mammary gland, the tight junctions of thealveolar epithelial cells are impermeable duringlactation, and thus allow milk to be stored betweennursing periods without leakage of milk components from the lumen. Nonetheless mammary epithelial tightjunctions are dynamic and can be regulated by a numberof stimuli. Tight junctions of the mammary gland fromthe pregnant animal are leaky, undergoing closure around parturition to become the impermeabletight junctions of the lactating animal. Milk stasis,high doses of oxytocin, and mastitis have been shown toincrease tight junction permeability. In general changes in tight junction permeability in themammary gland appear to be the results of a state changeand not assembly and disassembly of tight junctions.Both local factors, such as intramammary pressure and TGF-beta, and systemic factors, such asprolactin, progesterone, and glucocorticoids, appear toplay a role in the regulation of mammary tightjunctions. Finally, the tight junction state appears to be closely linked to milk secretion. Anincrease in tight junction permeability is accompaniedby decrease in the milk secretion rate, and conversely,a decrease in tight junction permeability is accompanied by an increase in the milk secretionrate.