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Cholesterol Transport and Regulation in the Mammary Gland

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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.

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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

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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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  1. Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, Buehlstrasse 28, 3012, Bern, Switzerland

    Edgar C. Ontsouka & Christiane Albrecht

  2. Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland

    Edgar C. Ontsouka & Christiane Albrecht

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Ontsouka, E.C., Albrecht, C. Cholesterol Transport and Regulation in the Mammary Gland. J Mammary Gland Biol Neoplasia 19, 43–58 (2014). https://doi.org/10.1007/s10911-014-9316-x

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