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Serotonin regulates mammary gland development via an autocrine-paracrine loop

Item Type:Article
Title:Serotonin regulates mammary gland development via an autocrine-paracrine loop
Creators Name:Matsuda, M. and Imaoka, T. and Vomachka, A.J. and Gudelsky, G.A. and Hou, Z.Y. and Mistry, M. and Bailey, J.P. and Nieport, K.M. and Walther, D.J. and Bader, M. and Horseman, N.D.
Abstract:Mammary gland development is controlled by a dynamic interplay between endocrine hormones and locally produced factors. Biogenic monoamines (serotonin, dopamine, norepinephrine, and others) are an important class of bioregulatory molecules that have not been shown to participate in mammary development. Here we show that mammary glands stimulated by prolactin (PRL) express genes essential for serotonin biosynthesis (tryptophan hydroxylase [TPH] and aromatic amine decarboxylase). TPH mRNA was elevated during pregnancy and lactation, and serotonin was detected in the mammary epithelium and in milk. TPH was induced by PRL in mammosphere cultures and by milk stasis in nursing dams, suggesting that the gene is controlled by milk filling in the alveoli. Serotonin suppressed β-casein gene expression and caused shrinkage of mammary alveoli. Conversely, TPH1 gene disruption or antiserotonergic drugs resulted in enhanced secretory features and alveolar dilation. Thus, autocrine-paracrine serotonin signaling is an important regulator of mammary homeostasis and early involution.
Keywords:Aromatic-L-Amino-Acid Decarboxylases, Autocrine Communication, Caseins, Cultured Cells, Developmental Gene Expression Regulation, Dialysis, Drug Dose-Response Relationship, Drug Interactions, Epithelial Cells, Fenclonine, Histology, Human Mammary Glands, Hydroxyindoleacetic Acid, Immunohistochemistry, Inbred C57BL Mice, In Situ Hybridization, Knockout Mice, Lactalbumin, Messenger RNA, Methysergide, Milk, Milk Proteins, Molecular Cloning, Mucins, Newborn Animals, Organ Culture Techniques, Paracrine Communication, Pregnancy, Prolactin, Reverse Transcriptase Polymerase Chain Reaction, Serotonin, Serotonin Antagonists, Time Factors, Tryptophan Hydroxylase, Animals, Mice
Source:Developmental Cell
ISSN:1534-5807
Publisher:Cell Press (U.S.A.)
Volume:6
Number:2
Page Range:193-203
Date:1 January 2004
Official Publication:https://doi.org/10.1016/S1534-5807(04)00022-X
PubMed:View item in PubMed

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