Regulation of VEGF and VEGF receptor expression in the rodent mammary gland during pregnancy, lactation, and involution

Vascular endothelial growth factors (VEGFs) are endothelial cell-specific m itogens with potent angiogenic and vascular permeability-inducing propertie s, VEGF, VEGF-C, and VEGFRs -1, -2, and -3 were found to be expressed in po st pubertal (virgin) rodent mammary glands. VEGF was increased during pregn ancy (5-fold) and lactation (15-19-fold). VEGF-C was moderately increased d uring pregnancy and lactation (2- and 3-fold respectively), VEGF levels wer e reduced by approximately 75% in cleared mouse mammary glands devoid of ep ithelial components, demonstrating that although the epithelial component i s the major source of VEGF, approximately 25% is derived from stroma, This was confirmed by the findings (a) that VEGF transcripts were expressed pred ominantly in ductal and alveolar epithelial cells, and (b) that VEGF protei n was localized to ductal epithelial cells as well as to the stromal compar tment including vascular structures. VEGF was detected in human milk, Final ly, transcripts for VEGFRs -2 and -3 were increased 2-3-fold during pregnan cy, VEGFRs -1, -2 and -3 were increased 2-4-fold during lactation, and VEGF Rs -2 and -3 were decreased by 20-50% during involution, These results poin t to a causal role for the VEGF ligand-receptor pairs in pregnancy-associat ed angiogenesis in the mammary gland, and suggest that they may also regula te vascular permeability during lactation. (C) 2000 Wiley-Liss, Inc.