Human Milk Synthesis and Secretion
June 20, 2022
Where are the constituents in human milk we have discussed made and how are they secreted into the milk space? Remember that the lactocyte is the milk making powerhouse.
Here is a drawing of a lactocyte. The apical membrane of the lactocyte is the side next to the lumen of the milk (highlighted in the picture in yellow). The basement membrane of the lactocyte is on the other side.
Five pathways or routes of secretion have been identified.
Four are transcellular (meaning the transfer of the substance occurs through the lactocyte)
One is paracellular (meaning the transfer of the substance is not through the lactocyte but between lactocytes)
Let’s look at the the five pathways. This is a bit confusing, read it and try to get the general idea. (Reference 1)
Exocytosis of secretory vesicles pathway
The primary mechanistic secretion of constituents of human milk is by exocytosis. The components are packaged into secretory vesicles and transported to the apical plasma membrane of the lactocytes where fusion takes place, resulting in the expulsion of the contents from the apical membrane. (Reference 2)
Most proteins in human milk rely on this pathway. The proteins are made by the nucleus and Golgi apparatus in the lactocyte from amino acid precursors. Small vesicles bud off the Golgi apparatus, make their way through the cytoplasm to the apical membrane, and are spewed out into the milk lumen.
The manufacturing of lactose and human milk oligosaccharides (HMOs) also use this pathway. The substrates needed to make lactose are transported into the Golgi apparatus of the lactocyte and there, lactose is made by the enzyme lactose synthase. Then they are packaged into secretory vesicles, delivered to the apical membrane, and secreted into the milk lumen. (Reference 2)
Lipid secretion pathway
“Milk lipids can either be synthesized within the gland or imported from the blood stream, where they are either derived from the immediate diet or from mobilized body fat.” (Reference 2)
Free fatty acids find their way into the endoplasmic reticulum of the lactocyte where they are linked to a molecule of glycerol to make a triglyceride. These lipid droplets weave their way to the apical membrane and are engulfed by the membrane and popped out into the lumen. This differs from the exocytosis of secretory vesicles in that the fat globule is total encased in apical membrane before it spews into the milk lumen, thus providing the milk fat globular membrane (MFGM). (Reference 3 for the image shown below.)
Eccrine secretion of water and minerals
This pathway uses simple diffusion or transport proteins to move substances through the apical membrane. Examples here are water, sodium, potassium and chloride.
Substances get into the cytoplasm of the lactocyte, weave through it to the apical membrane, and are released. Examples here are antibodies like Secretory IgA.
This occurs at times when the junctions between the lactocytes are loose (identified as open in the picture below). This occurs during pregnancy, in the very early days after birth, with mastitis, and with weaning.
1. Core Curriculum for Interdisciplinary Lactation Care. Edited by Suzanne Hetzel Campbell, Judith Lauwers, Rebecca Mannel, and Becky Spencer. LEAARC (Lactation Education Accreditation and Approval Review Committee). Jones & Bartlett Learning. 2019
2. Hale & Hartmann’s Textbook of Human Lactation, First Edition. Thomas W. Hale and Peter E. Hartmann, editors. Springer Publishing Company. 2017
3. Illustration by Erik Domellof. The Journal of Pediatrics. 2016;173(Supplement):S60-S65.