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Effect of Lactogenic Stimuli and Serotonin on Secretory Activation of Bovine Mammary Epithelial Cells (BMEC)
Author(s) -
Stiening Chad Michael,
Abdallah Mheni Ben,
Hoying James B,
Collier Robert Joseph
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a616-b
Subject(s) - microbiology and biotechnology , endocrinology , medicine , serotonin , biology , chemistry , receptor , biochemistry
Culturing primary BMEC in a collagen gel with insulin‐like growth factor I (IGF‐I) and epidermal growth factor enables three‐dimensional ductal growth and branching morphogenesis. We evaluated effects of structural (gel release) and hormonal (prolactin, PRL) stimuli on BMEC gene expression in presence of IGF‐1 and cortisol. Gel release and PRL independently regulated a wide variety of genes involved in tissue remodeling, structural reorganization and lactogenesis. When the two stimuli were applied together, a smaller set of genes associated with secretory activation (caseins, alpha lactalbumin, calmodulin, xanthine dehydrogenase, galectin, milk lysozyme, galactokinase, Ig‐family proteins, TGF‐beta), intracellular trafficking (dynactin, spectrin, tubulin, dynein, thymosin‐beta4, synaptophysin), epithelial tight junctions (claudin) and interactions (cadherins), and extracellular matrix remodeling (MMP, esterase) were regulated. We then evaluated effects of serotonin on BMEC secretion activation. We found that PRL up‐regulates TPH‐1, the rate limiting enzyme for serotonin synthesis, and that serotonin down‐regulates expression of α‐lactalbumin. Furthermore, when serotonin receptors are blocked with methysergide, transcription of both casein and α‐lactalbumin is enhanced. A model is proposed whereby PRL induces the serotonin biosynthetic pathway, leading to negative feedback of serotonin through its receptor(s) causing down‐regulation of α‐lactalbumin which reduces the rate of milk secretion.