Mammary mechanisms for lactoferrin: interactions with IGFBP-3.

• Main Author: Baumrucker C.R.
• Format: Article
• Language: English
• Published: Presses Agronomiques de Gembloux 2000-01-01
• Series: Biotechnologie, Agronomie, Société et Environnement
• Subjects: dairy-cows; mammary-glands; lactoferrin; insulin-like-growth-factor; animal-glands; body-parts; bovidae; bovinae; cattle; cows; dairy-cattle; domestic-animals; exocrine-glands; globulins; glycoproteins; growth-factors; hormones; lactoglobulins; livestock; mammals; proteins; ruminants; useful-animals
• Online Access: http://www.pressesagro.be/base/text/v4n1/5.pdf

Lactoferrin (Lf) is an iron-binding protein found in high concentrations in mammary secretions but synthesized by many tissues. Bovine mammary tissue secretes microg/ml mass of Lf in milk, but during involution and prepartum periods, 20-80 mg per ml concentrations may be observed. While a number of functions have been ascribed to lactoterrin, only the antimicrobial and lymphocyte interactions have compelling experimental evidence of support. We report a new finding that lactoferrin binds to insulin-like growth factor binding protein-3 (IGFBP-3) and not to other mammary secreted IGFBPs (IGFBP-2, -4. and -5). Furthermore, bovine Lf(bLf) is found associated with membranes of mammary cells. We demonstrate that bovine Lf competes with IGF for binding to IGFBP-3 with ED50 competition of 3 microg per ml and displacement of 1 mg per ml to monomeric bLf. The tetrameric form that is favored by high concentrations of Lf and calcium, does not appear to bind IGFBP-3. Both IGFBP-3 and Lf have nuclear localization sequences that are reported to he key components of nuclear localization of proteins. We demonstrate that extracellular IGFBP-3 binds to membrane Lf and that Lf is the key to the entry of IGFBP-3 to mammary cellular nucleus. Additionally, we have shown that the internalization of Lf requires the presence of retinoids that also induces both IGFBP-3 and Lf synthesis in primary cultures of bovine mammary epithelial cells. We hypothesize a new role for Lf in the regulation and integration into the IGF System.