Nutrient Transport in the Mammary Gland: Calcium, Trace Minerals and Water Soluble Vitamins

Abstract

Milk nutrients are secreted by epithelial cells in the alveoli of the mammary gland by several complex and highly coordinated systems. Many of these nutrients are transported from the blood to the milk via transcellular pathways that involve the concerted activity of transport proteins on the apical and basolateral membranes of mammary epithelial cells. In this review, we focus on transport mechanisms that contribute to the secretion of calcium, trace minerals and water soluble vitamins into milk with particular focus on the role of transporters of the SLC series as well as calcium transport proteins (ion channels and pumps). Numerous members of the SLC family are involved in the regulation of essential nutrients in the milk, such as the divalent metal transporter-1 (SLC11A2), ferroportin-1 (SLC40A1) and the copper transporter CTR1 (SLC31A1). A deeper understanding of the physiology and pathophysiology of these transporters will be of great value for drug discovery and treatment of breast diseases.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation

“…Little information is available with regard to the mechanisms of vitamin secretion into breast milk (35). Water-soluble vitamins are thought to be actively secreted involving members of the solute carrier (SLC) and ATP-binding cassette (ABC) family; breast cancer–resistant protein (BCRP) is associated with riboflavin secretion, vitamin B-12 uptake might be partly dependent on a receptor-mediated system, and thiamin transporters THTR1 and THTR2 may be involved in thiamin secretion.…”

“…Water-soluble vitamins are thought to be actively secreted involving members of the solute carrier (SLC) and ATP-binding cassette (ABC) family; breast cancer–resistant protein (BCRP) is associated with riboflavin secretion, vitamin B-12 uptake might be partly dependent on a receptor-mediated system, and thiamin transporters THTR1 and THTR2 may be involved in thiamin secretion. The transport mechanisms involved with niacin and vitamin B-6 are unknown (11, 35). The regulation of fat-soluble vitamins A and E appears to occur through a specific transport system independent from lipid transfer, but the mechanisms involved have not been revealed (36, 37).…”

Physiology of milk secretion

“…Moreover, the activity of some of these transporters, such as Ctr1 and ATP7A for copper and Zip3 for zinc, has been shown to be up-regulated by PRL, which induces their targeting to the BPM. Adequate supply of trace elements from milk is crucial to ensure neonate survival and both their uptake from blood and release in milk are tightly regulated by MECs, so that trace element concentrations remain remarkably stable, independently of the mother's diet [44].…”

“…The presence of calcium channels has been described in the BPM and some intracellular membranes of MECs [44,45], while the intracellular compartmentalization of calcium depends on cytoplasmic binding proteins. In milk, calcium is found associated with casein micelles (~20%), free ionized or non-ionized (~32%) or complexed to inorganic anions such as phosphate and citrate (~46%).…”

Riboflavin uptake transporter Slc52a2 (RFVT2) is upregulated in the mouse mammary gland during lactation

“…Breast milk is a complex mixture of macronutrients (e.g., proteins, carbohydrates, and lipids)-some of which function as bioactive factors-and micronutrients such as vitamins (1). Despite our extensive knowledge of the nutritional composition of breast milk, we still have a very poor understanding of transport mechanisms responsible for transferring many of these nutrients into breast milk and reasons for individual variations (17).…”