Serotonin Regulates Mammary Gland Development via an Autocrine-Paracrine Loop

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 developme...

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Bibliographic Details
Published in:Developmental cell 2004-02, Vol.6 (2), p.193-203
Main Authors: Matsuda, Manabu, Imaoka, Tatsuhiko, Vomachka, Archie J, Gudelsky, Gary A, Hou, Zhaoyuan, Mistry, Meenakshi, Bailey, Jason P, Nieport, Kathryn M, Walther, Diego J, Bader, Michael, Horseman, Nelson D
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
aromatic amine decarboxylase
Aromatic-L-Amino-Acid Decarboxylases - genetics
Aromatic-L-Amino-Acid Decarboxylases - metabolism
Autocrine Communication - drug effects
Autocrine Communication - physiology
Caseins - genetics
Caseins - metabolism
Cells, Cultured
Cloning, Molecular
Dialysis
Dose-Response Relationship, Drug
Drug Interactions
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Female
Fenclonine - pharmacology
Gene Expression Regulation, Developmental
Histology
Humans
Hydroxyindoleacetic Acid - metabolism
Immunohistochemistry
In Situ Hybridization
Lactalbumin - genetics
Lactalbumin - metabolism
Mammary Glands, Human - cytology
Mammary Glands, Human - drug effects
Mammary Glands, Human - growth & development
Methysergide - pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Milk - metabolism
Milk Proteins - genetics
Milk Proteins - metabolism
Mucins - genetics
Mucins - metabolism
Organ Culture Techniques
Paracrine Communication - drug effects
Paracrine Communication - physiology
Pregnancy
Prolactin - deficiency
Prolactin - genetics
Prolactin - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
Serotonin - physiology
Serotonin Antagonists - pharmacology
Time Factors
TPH1 gene
tryptophan hydroxylase
Tryptophan Hydroxylase - genetics
Tryptophan Hydroxylase - metabolism
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Summary: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.
ISSN:1534-5807
1878-1551
DOI:10.1016/S1534-5807(04)00022-X