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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Detalles Bibliográficos
Autores: Tundidor, Isabel, Seijo Vila, Marta, Blasco-Benito, Sandra, Rubert-Hernández, María, Moreno-Bueno, Gema, Bindila, Laura, Fernández de la Rosa, Rubén, Guzmán Pastor, Manuel, Sánchez García, María Cristina, Pérez Gómez, Eduardo
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/102453
Acceso en línea:https://hdl.handle.net/20.500.14352/102453
Access Level:acceso abierto
Palabra clave:577.1
Fatty acid amide hydrolase
Adult mammary gland
Bioquímica (Biología)
2403 Bioquímica
Descripción
Sumario: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 CB1 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.