Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation

Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentia...

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Published inCell death discovery Vol. 10; no. 1; p. 12
Main Authors Tundidor, Isabel, Seijo-Vila, Marta, Blasco-Benito, Sandra, Rubert-Hernández, María, Moreno-Bueno, Gema, Bindila, Laura, de la Rosa, Rubén Fernández, Guzmán, Manuel, Sánchez, Cristina, Pérez-Gómez, Eduardo
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 06.01.2024
Springer Nature B.V
Nature Publishing Group
Subjects
631/136/142
631/136/2435
Anandamide
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cannabinoid CB1 receptors
Cell Biology
Cell Cycle Analysis
Cell differentiation
Cell fate
Cell proliferation
Central nervous system
Endocannabinoid system
Epithelial cells
Fatty acids
Fatty-acid amide hydrolase
Lactation
Life Sciences
Mammary gland
Milk production
Puberty
Stem Cells
Therapeutic targets
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Summary:Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB 1 receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits.
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ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-023-01788-1