title: Regulation of mammary parenchymal growth by the fat pad in prepubertal dairy heifers: role of inflammation-related proteins.
abstract: In prepubertal heifers, the mammary parenchyma consists of epithelial and myoepithelial cells growing within a mammary fat pad (MFP). The MFP produces IGF-I that stimulates epithelial cell proliferation. In other species, adipose tissue expansion induces inflammation-related proteins (IRP), such as tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-1beta transforming growth factor beta, monocyte chemoattractant protein 1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1). The MFP production of IRP may influence mammary development because they impair not only insulin but also IGF-I actions. Moreover, the MFP expansion seen with development and increased nutrition coincides with reduced parenchymal growth. Our first objective was to identify IRP capable of altering proliferation of bovine mammary epithelial cells. TNFalpha, but neither IL-6, IL-1beta MCP-1 nor PAI-1, inhibited basal and IGF-I-stimulated proliferation in MAC-T cells and primary cells isolated from heifers. Our second objective was to determine whether MFP expression of IRP changed in a manner consistent with inhibition of parenchymal growth. MFP expression was measured from 100 to 350 kg body weight (experiment 1) or at 240 kg body weight (experiment 2) in dairy heifers offered restricted or high planes of nutrition. In experiment 1, neither nutrition nor development altered MFP expression of TNFalpha. Nutrition increased MCP-1 and PAI-1 but only before MFP expansion and after cessation of allometric parenchymal growth. In experiment 2, nutrition increased TNFalpha and PAI-1, but not MCP-1. Thus, MFP expansion increases IRP production in cattle, but this is unlikely to contribute to reduced parenchymal growth observed with development or increased nutrition.
authors.affiliation: Department of Animal Science, Cornell University, 259 Morrison Hall, Ithaca, New York 14853, USA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thorn
authors.forename: Stig
authors.initials: S
authors.lastname: Purup
authors.forename: Mogens
authors.initials: M
authors.lastname: Vestergaard
authors.forename: Kris
authors.initials: K
authors.lastname: Sejrsen
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Meyer
authors.forename: Micheal E
authors.initials: ME
authors.lastname: Van Amburgh
authors.forename: Yves R
authors.initials: YR
authors.lastname: Boisclair
mesh_terms: D000273:Adipose Tissue / Q000254:growth & development*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002417:Cattle; D002461:Cell Line, Transformed; D018932:Chemokine CCL2 / Q000235:genetics / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000494:pharmacology; D012741:Sexual Maturation / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I