Abstract

Milk is a nutritionally complete, immunologically important, developmental regulator of all major physiological systems in the neonate. From neonatal birth to weaning, the composition of milk changes with the mother's diet and environment, and with the needs of the offspring. All of the constituents of milk are either synthesized in the mammary gland or transported across the epithelial barrier from other sources. Unique hallmarks of milk-secreting cells include the assembly and secretion of lipid droplets coated with cellular membranes, synthesis of lactose, which indirectly regulates the secretion of water, and the assembly of caseins with calcium and phosphate into micellar aggregates. At least five major pathways have been identified: (1) secretion of membrane-coated lipid droplets from the apical surface; (2) packaging of most skim milk proteins, lactose, ions, and water in secretory vesicles, followed by secretion from the apical plasma membrane by exocytosis; (3) transport of proteins, including immunoglobulins and peptide hormones, from other sources by transcytosis; (4) equilibration of ions and water across the interstitial space, cell cytoplasm, and milk by specific transporters; and (5) paracellular transit of material between cells when the epithelial tight junctions are permeable, for example, during late pregnancy, late lactation, and at times of bacterial inflammation. In addition, membrane-bounded vesicles containing cytoplasmic proteins, called “exosomes”, are released from the milk-secreting cell but the underlying mechanisms of this secretion are poorly understood.

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