The protein fraction of milk contains several components with physiological significance for the development of the newborn. Among them, immunomodulatory peptides and lactoferrin exemplify the complexity of biologically active substances of milk. Immunomodulatory peptides have latent activity within the native protein and are generated after proteolysis during gastrointestinal transit. Once they are generated, they modulate mucosal immunity, possibly by guiding the local immune system until it develops its full functionality. Lactoferrin is another milk bioactive compound with nutritional and health promoting properties; it modulates the microbial intestinal environment, displays anti-microbial activity against various pathogens and stimulates the establishment of beneficial microflora. The following overview focuses on the importance of immunomodulatory peptides and lactoferrin for the maturation of intestine and immune system that are functionally immature in the newborn.

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Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine the role of insulin signaling in mammary development in pregnancy using a mouse with a floxed insulin receptor (IR) crossed with a mouse expressing Cre specifically in the mammary gland. In the mammary glands of these IR fl/fl Cre ϩ mice, expression of IR is significantly diminished throughout development. Glands from these mice had 50% fewer alveoli at midpregnancy; casein and lipid droplets were diminished by 60 and 75%, respectively, indicating a role for IR both in alveolar development and differentiation. In an acinar preparation from mammary epithelial cells (MEC) isolated from pregnant mice, insulin stimulated lumen formation, mammary cell size, acinar size, acinar casein content, and the formation of lipid droplets with a Km of ϳ1.7 nM. IGF-I and IGF-II had no effect at concentrations below 50 nM, and a function blocking antibody to the IGF type 1 receptor did not alter the response to insulin. We conclude that insulin interacting with IR is essential for mammary differentiation during murine pregnancy. Using array analysis, we then examined the expression of genes up-or downregulated Ͼ1.5-fold in the IR fl/fl Cre ϩ MECs, finding significant downregulation of differentiation specific genes and upregulation of cell cycle and extracellular matrix genes. We conclude that insulin fosters differentiation and may inhibit cell proliferation in the mammary gland of the midpregnant mouse. mammary development; acinar culture THE HORMONAL REGULATION OF mammary development and milk secretion has received extensive research attention in the last half-century (14), and the roles of the major sex steroid hormones, estrogen and progesterone (P4), as well as the lactogenic hormones prolactin (PRL) and hydrocortisone (HC) are quite well understood (26,28). Insulin is another story. It is difficult to ablate the insulin-secreting pancreatic islets, or to increase plasma insulin, without seriously impairing the metabolism of the whole animal; for this reason, alternative approaches have been necessary to elucidate the role of insulin in mammary gland development. The same concern extends to the use of transgenic and knockout mice that have been used to great effect to study steroid hormones. Although genetically modified mice can be used for studying the insulin system, as we will see the experimental design is crucial if complicating systemic effects are to be avoided.Much early data demonstrated a role for insulin in maintenance of milk secretion in the lactating animal (1,3,15,18,19,22,25,33,35). The earliest studies showed that insulin stimulated lipid synthesis in mammary slices from lactating ruminants (13). However, in these experiments, effects on mammary epithelial and adipose tissues were not distinguished. Furthermore, in the dairy cow, raising insulin levels from 0.25 to 1.3 nM in the context of glucose clamp experiments had no effect on milk production (21), suggesting that the lactating gland of the ...

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity. Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P < 0.01) reduced OTA cytotoxicity, lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that α-tocopherol supplementation may counteract short-term OTA toxicity, supporting its defensive role in the cell membrane.