Abstract

To investigate the role of low-density lipoprotein (LDL) in the delivery of cholesterol to the mammary gland during pregnancy and lactation, we examined the distribution of radioactivity from 125I-tyramine cellobiose-LDL injected into the tail vein of female mice at various stages of the reproductive cycle. Changes in the proportion of isotope taken up by the mammary gland largely reflected the increased weight of the gland in pregnancy and lactation. In addition, during lactation, radioactivity was found in the milk and was associated with a protein of the molecular weight of apoB-100. Quantitatively similar results were obtained with mice homozygous for disruption of the LDL receptor gene (LDLR null). Analysis of endogenous lipoproteins showed that the milk lipoprotein particles were denser than the corresponding serum lipoproteins and largely depleted of triglyceride and cholesterol. Using fluorescence microscopy we visualize the sorting of apoB protein from the LDL lipid phase at the basal surface of the mammary epithelial cell of both wild-type and LDLR-null mice. Our findings provide evidence that the mammary epithelium of the lactating mouse is able to take up LDL from the plasma by a non-LDLR-mediated process. An apoB-containing particle from which the cholesterol has been removed is transferred into milk.—Monks, J., P. U. Huey, L. Hanson, R. H. Eckel, M. C. Neville, and S. Gavigan. A lipoprotein-containing particle is transferred from the serum across the mammary epithelium into the milk of lactating mice. J. Lipid Res. 2001. 42: 686–696.

Highlights

  • To investigate the role of low-density lipoprotein (LDL) in the delivery of cholesterol to the mammary gland during pregnancy and lactation, we examined the distribution of radioactivity from 125I-tyramine cellobiose-LDL injected into the tail vein of female mice at various stages of the reproductive cycle

  • Because these reports predate any understanding of the mechanisms of cellular cholesterol trafficking, we initiated a study of low-density lipoprotein (LDL) metabolism in the mouse mammary gland

  • To determine whether the low-density lipoprotein receptor (LDLR) is involved in this uptake, we examined the interaction of labeled LDL with the mammary gland of normal and LDLR-null mice

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Summary

Introduction

To investigate the role of low-density lipoprotein (LDL) in the delivery of cholesterol to the mammary gland during pregnancy and lactation, we examined the distribution of radioactivity from 125I-tyramine cellobiose-LDL injected into the tail vein of female mice at various stages of the reproductive cycle. Using fluorescence microscopy we visualize the sorting of apoB protein from the LDL lipid phase at the basal surface of the mammary epithelial cell of both wild-type and LDLR-null mice. A lipoprotein-containing particle is transferred from the serum across the mammary epithelium into the milk of lactating mice. The best understood pathway for cholesterol uptake by cells utilizes the LDL receptor (LDLR), shown by Goldstein et al [7] to recognize the apolipoprotein (apo)B protein moiety of LDL [8]. The lipoprotein is targeted to the lysosomes for degradation of both the protein and lipid components Cholesterol released by this process is available for membrane synthesis or storage as cholesterol ester. More recently it has been shown that some cells, including hepatocytes and steroidogenic cells, accumulate cholesterol from high-density lipoprotein (HDL) and LDL via a selective uptake pathway utilizing scavenger receptors (9 – 13).

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