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Cholesterol Transport and Regulation in the Mammary Gland

  • Edgar C. Ontsouka
  • Christiane AlbrechtEmail author
Article

Abstract

The milk-producing alveolar epithelial cells secrete milk that remains after birth the principal source of nutrients for neonates. Milk secretion and composition are highly regulated processes via integrated actions of hormones and local factors which involve specific receptors and downstream signal transduction pathways. Overall milk composition is similar among mammalian species, although the content of individual constituents such as lipids may significantly differ from one species to another. The milk lipid fraction is essentially composed of triglycerides, which represent more than 95 % of the total lipids in human and commercialized bovine milk. Though sterols, including cholesterol, which is the major milk sterol, represent less than 0.5 % of the total milk lipid fraction, they are of key importance for several biological processes. Cholesterol is required for the formation of biological membranes especially in rapidly growing organisms, and for the synthesis of sterol-based compounds. Cholesterol found in milk originates predominantly from blood uptake and, to a certain extent, from local synthesis in the mammary tissue. The present review summarizes current knowledge on cellular mechanisms and regulatory processes determining intra- and transcellular cholesterol transport in the mammary gland. Cholesterol exchanges between the blood, the mammary alveolar cells and the milk, and the likely role of active cholesterol transporters in these processes are discussed. In this context, the hormonal regulation and signal transduction pathways promoting active cholesterol transport as well as potential regulatory crosstalks are highlighted.

Keywords

ABC transporters Cholesterolemia Cholesterol transport Hormonal regulation Lipid secretion Mammary gland Milk lipid composition Signaling pathways 

Abbreviations

ABC transporter

ATP-binding cassette transporter

ACAT

Acyl-coenzyme A: cholesterol acyltransferase

ApoA-I

Apolipoprotein A-I

CEH

Cholesteryl ester hydrolase

CLD

Cytoplasmic lipid droplets

HDL

High density lipoprotein

HMG-CoA

3-hydroxy-3-methylglutaryl-CoA

HSL

Hormone-sensitive lipase

JAK-2

Janus-kinase-2

LAL

Lysosomal acid lipase

LDL

Low density lipoprotein

LPL

Lipoprotein lipase

LXR

Liver X receptor

MAPK

Mitogen-activated protein kinase

MEC

Alveolar mammary epithelial cell

MFG

Milk fat globule

NPC

Niemann-Pick type C

OSBP

Oxysterol-binding protein

ORP

OSBP-releated protein

PPAR

Peroxisome proliferator-activated receptor

PREB

Prolactin regulatory element binding

SR-BI

Scavenger receptor class B type I

SREBP

Sterol response element binding protein

VLDL

Very low density lipoprotein

Notes

Acknowledgments

The present paper was supported by the Swiss National Science Foundation through the National Centre of Competence in Research TransCure. The authors thank Xiao Huang for her major contribution in the design of the figures.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Biochemistry and Molecular Medicine, Faculty of MedicineUniversity of BernBernSwitzerland
  2. 2.Swiss National Center of Competence in Research, NCCR TransCureUniversity of BernBernSwitzerland

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