Serotonin regulates mammary gland development via an autocrine-paracrine loop
Serotonin regulates mammary gland development via an autocrine-paracrine loop
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DOI：
10.1016/s1534-5807(04)00022-x
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发表时间：
2004-02-01
影响因子：
11.8
通讯作者：
Horseman, ND
中科院分区：
文献类型：
--
作者：
Matsuda, M;Imaoka, T;Horseman, ND
乳腺发育受内分泌激素和局部产生因子的动态相互作用控制。生物单胺（血清素、多巴胺、去甲肾上腺素等）是一类重要的生物调节分子，但尚未被证明参与乳腺发育。本研究表明，泌乳素（PRL）刺激乳腺表达5 -羟色胺生物合成所必需的基因（色氨酸羟化酶（TPH）和芳香胺脱羧酶）。妊娠和哺乳期TPH mRNA升高，乳腺上皮和乳汁中检测到血清素。在乳腺球培养物中PRL和在哺乳池中乳瘀诱导TPH，提示该基因受肺泡内乳淤积的控制。血清素抑制β -酪蛋白基因表达，引起乳腺泡萎缩。相反，TPH1基因破坏或抗血清素能药物导致分泌特征增强和肺泡扩张。因此，自分泌-旁分泌血清素信号是乳腺稳态和早期退化的重要调节因子。
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 beta-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.