Induction of
protein expression in a tissue-specific manner by gene transfer over-expression techniques has been one means to define the function of a
protein in a biological paradigm. Studies with
retinoid reporter constructs transfected in mammary cell lines suggests that
lactoferrin (Lf) affects
retinoid signaling pathways and alters apoptosis. We tested the effects and interactions of over-expressed mammary-specific human
lactoferrin (hLf) and dietary
retinol palmitate on lactation and mammary gland development in mice. Increased
retinol palmitate in the diet increased daily
retinol equivalents (RE) to 2.6-fold over the normal mouse control diet. Transgene (Tg) expression in the dam fed control diet depressed pup
weight gain. Severe depression of pup
weight gain was observed when homozygote
TgTg dams were fed the RE diet. Normal
weight gain was restored when pups were placed with a wild type dam fed the RE diet; conversely, normal growing pups from the wild type dams showed declining
weight gains when fostered to the
TgTg RE-fed dams. Northern analysis of mammary
tissue extracts showed a reduction in WAP and an increase in
IGFBP-3 mRNA that was associated with the presence of the transgene. Histological evaluation of 3 days lactating mammary tissue showed mammary epithelial cells from
TgTg animals contained excessive secretory products, suggesting a block in cellular secretion mechanisms. In addition, the mammary cells displayed a cellular apical membrane puckering that extended into the alveoli lumens. These studies demonstrate an in vivo interaction of Tg-hLf expression and dietary
retinoids in mouse mammary glands. While normal mammary gland physiology may not be representative by these experiments because high Lf concentrations during early lactation are abnormal, the demonstrated biological interaction suggests that typical periods of high Lf concentrations may have impact upon developing and involuting mammary glands.