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oai:docta.ucm.es:20.500.14352/1024532024-03-22T01:12:13Zcom_20.500.14352_14col_20.500.14352_15

Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation 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 577.1 Fatty acid amide hydrolase Adult mammary gland Bioquímica (Biología) 2403 Bioquímica 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. Instituto de Salud Carlos III (ISCIII)/Unión Europea Ministerio de Economía y Competitividad (MINECO) Depto. de Bioquímica y Biología Molecular Fac. de Ciencias Biológicas TRUE pub 2024-03-21T13:05:32Z 2024-03-21T13:05:32Z 2024-01-06 journal article VoR https://hdl.handle.net/20.500.14352/102453 XXXX-XXXX 10.1038/s41420-023-01788-1 2058-7716 eng PI17/00041 and PI20/00590 PFIS fellowship Tundidor I, Seijo-Vila M, Blasco-Benito S, Rubert-Hernández M, Moreno-Bueno G, Bindila L, de la Rosa RF, Guzmán M, Sánchez C, Pérez-Gómez E. Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation. Cell Death Discov. 2024 Jan 6;10(1):12. doi: 10.1038/s41420-023-01788-1. PMID: 38184644; PMCID: PMC10771414. open access application/pdf Springer Nature