Lactocytes: location and function
Lactocytes are the milk-secreting cells in the mammary glands of female mammals. These cuboidal cells are located in the alveoli of a lactating breast where they are surrounded by the myoepithelial cells (cells from ducts of the lobules). The contractile motion of the myoepithelial cells releases milk into the lobules which are radially organized around the nipple. Post pregnancy, the pituitary hormone prolactin drives the production and distribution of the breast milk supply. During the latent period (the time when an infant begins suckling), a neuroendocrine reflex is triggered in the sensory nerve fibres near the areolar region which initiates the secretion of milk from lactocytes into the alveoli. The female body prepares itself during pregnancy for lactation by facilitating the development and proliferation of alveoli lined with milk-secreting lactocytes (1).
Besides being a primary alveolar cell subtype, lactocytes express specific markers such as cytokeratin 18 (CK18) which serve as a potential prognostic marker for several cellular processes such as apoptosis, mitosis, cellular signalling etc. (2). They are also responsible for the synthesis of milk proteins such as α-lactalbumin and ß-casein (3).
Hormonal regulation of lactocytes
The production of milk in the mammary glands and its secretion from lactocytes is tightly regulated by the hormonal milieu. Morphological differentiation of alveolar cells into lactocytes (secretory mammary epithelial cells (MECs)) is a concomitant process with progesterone and estrogen withdrawal along with prolactin release after parturition. This synchronization renders the differentiated epithelium notably efficient in coordinating the production and distribution of various constituents of milk for the onset of milk secretion (4). Once an infant is born after a full-term pregnancy, the lactocytes close the tight junctions of the epithelium and restrict the passage of sodium and chloride ions and small molecules to facilitate lactation and milk secretion (5). The reproductive hormones such as prolactin and metabolic hormones, e.g., glucocorticoids, insulin, thyroid hormone etc., can directly or indirectly influence the endocrine response of the lactocytes. This alteration significantly impacts the process of nutrient delivery to the mammary glands for milk production (6).
Other than milk production and secretion, lactocytes also possess the capability to control it when the breast is full. It does so with the help of a feedback inhibitor of lactation (FIL) polypeptide. This polypeptide is endogenously synthesized in the lactocytes and keeps a check on the synthesis and transport of milk through an autocrine feedback mechanism (7).
Major cell types of human breast milk and subclusters of lactocytes
Cells of human breast milk comprise two broad categories: probiotic bacteria and breast milk cells. Breast milk cells are further divided into breast-derived cells and cells derived from the blood. The lactocytes, myoepithelial cells, progenitor cells and stem cells belong to the breast-derived cells whereas immunological cells and hematopoietic stem cells originate from the blood. Immunological cells include cells such as monocytes, T cells, NK cells, B cells, neutrophils, eosinophils and immature granulocytes (8). Over the course of lactation, human breast epithelium undergoes a continuum of cell state dynamics. The largest subclusters of lactocytes, the secretory lactocytes, express markers (CHRDL2, CIDEA, ATP2C2) critical for metabolic processes and also contain genes for the biosynthesis of lipid and lactose (FBP1, ACACB). The second largest subcluster, LC1, is involved in the pathways-related establishment and maintenance of microtubule and cellular organization such as supporting cell-cell tight junctions and protein transport. These pathways are crucial in supporting the alveolar structures of the lactating breast (9). Everything considered, lactocytes form an indispensable component of human breast milk which requires further investigation for healthy lactation and milk production.
Recognizing and appreciating the labs working in this space
- The Human Milk Institute, University of California San Diego, USA. https://hmi.ucsd.edu/
- Vallier Lab, Max Planck Institute for Molecular Genetics, Berlin, Germany. https://www.molgen.mpg.de/4595564/vallier-lab
- Milk Research Lab, Boston Medical Center, Massachusetts, USA https://cheerequity.org/cheer-champions/milk-research-lab/ , X: @CHAMPSBF , Instagram: @cheerequity
- Rebecca Powell Laboratory, Icahn School of Medicine at Mount Sinai, New York, USA. https://labs.icahn.mssm.edu/rebecca-powell-lab/about-us/ , X: @MountSinaiNYC , LinkedIn: linkedin.com/in/rebecca-powell-32a23713a
- Human Milk and Nutrition Research Group at the University of Minnesota, USA. https://milkresearch.umn.edu/
- BIOMILQ, North Carolina, USA. https://www.biomilq.com/ , X: @biomilq
- Cambridge Lactation Lab, University of Cambridge, UK https://www.cambridgelactationlab.com/ , X: @AJ_Twigger , LinkedIn: linkedin.com/in/aleciajanetwigger
- RUSH NICU Human Milk Research Program, RUSH University. Chicago, Illinois, USA. https://www.rushu.rush.edu/research-rush-university/departmental-research/pediatrics-research/rush-nicu-human-milk-research-program , X: @RushUniversity , Instagram: @rushuniversity
References
- https://courses.lumenlearning.com/suny-ap2/chapter/lactation/
- Weng, Yu-Rong et al. “Biological functions of cytokeratin 18 in cancer.” Molecular cancer research : MCR vol. 10,4 (2012): 485–93. doi:10.1158/1541–7786.MCR-11–0222
- Twigger, Alecia-Jane et al. “Gene expression in breastmilk cells is associated with maternal and infant characteristics.” Scientific reports vol. 5 12933. 10 Aug. 2015, doi:10.1038/srep12933
- Pang, Wei Wei, and Peter E Hartmann. “Initiation of human lactation: secretory differentiation and secretory activation.” Journal of mammary gland biology and neoplasia vol. 12,4 (2007): 211–21. doi:10.1007/s10911–007–9054–4
- Kulski, J K, and P E Hartmann. “Changes in human milk composition during the initiation of lactation.” The Australian journal of experimental biology and medical science vol. 59,1 (1981): 101–14. doi:10.1038/icb.1981.6
- Brisken, Cathrin, and Bert O’Malley. “Hormone action in the mammary gland.” Cold Spring Harbor perspectives in biology vol. 2,12 (2010): a003178. doi:10.1101/cshperspect.a003178
- Peaker, M, and C J Wilde. “Feedback control of milk secretion from milk.” Journal of mammary gland biology and neoplasia vol. 1,3 (1996): 307–15. doi:10.1007/BF02018083
- Witkowska-Zimny M, Kaminska-El-Hassan E. Cells of human breast milk. Cell Mol Biol Lett. 2017 Jul 13;22:11. doi: 10.1186/s11658–017–0042–4. PMID: 28717367; PMCID: PMC5508878.
- Nyquist SK, Gao P, Haining TKJ, Retchin MR, Golan Y, Drake RS, Kolb K, Mead BE, Ahituv N, Martinez ME, Shalek AK, Berger B, Goods BA. Cellular and transcriptional diversity over the course of human lactation. Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2121720119. doi: 10.1073/pnas.2121720119. Epub 2022 Apr 4. PMID: 35377806; PMCID: PMC9169737.
About the author:
DR. SURUCHI PODDAR
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Poddar received a PhD in Biomedical Engineering from Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, India. She started her career as a postdoctoral researcher in 2020 with the Nanoscience Technology Center at the University of Central Florida, Orlando where she worked on a multi-organ human-on-a-chip system. Currently she is working on solid-state nanopore technology at Wake Forest University, North Carolina. When not working, she enjoys watching movies, cooking food and exploring new places, restaurants, attractions.
About the artists:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
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Contributing Artist The League of Extraordinary Celltypes, Sci-Illustrate Stories
Bruna received her Bachelor’s degree in Biological Sciences and her Master’s in Cellular and Molecular Biology from the University of Tuscia, Italy. She then pursued a PhD in Molecular Biology at the Max Planck Institute for Biology of Aging in Cologne, Germany.
Alongside her scientific career, she has nurtured a passion for the arts, exploring various crafts as hobbies, such as sculpture, embroidery, and digital drawing. These combined interests led her to create scientific graphics, and to use illustrations as a tool to communicate biology in a simpler and more accessible way.
Currently residing in Germany, Bruna continues to illustrate scientific concepts, with a particular focus on cover illustrations, some of which have been published in esteemed scientific journals.
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DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
