Age-related changes in the epithelial and stromal compartments of the mammary gland in normocalcemic mice lacking the vitamin D3 receptor.
Age-related changes in the epithelial and stromal compartments of the mammary gland in normocalcemic mice lacking the vitamin D3 receptor.
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DOI：
10.1371/journal.pone.0016479
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发表时间：
2011-01-26
期刊：
影响因子：
3.7
通讯作者：
Zinser GM
中科院分区：
文献类型：
--
作者：
Welsh J;Zinser LN;Mianecki-Morton L;Martin J;Waltz SE;James H;Zinser GM
维生素D3受体（VDR）在乳腺发育过程中通过抑制青春期的分支形态发生和调节妊娠、哺乳期和复归期间的分化和凋亡，起到负生长调节剂的作用。为了评估VDR在衰老乳腺中的作用，我们利用12、14和16个月大的VDR敲除（KO）和野生型（WT）小鼠来评估上皮和间质室的完整性、类固醇激素水平和信号通路。我们的数据表明，VDR消融与原发性乳腺导管扩张、第二和第三导管分支丧失以及乳腺脂肪垫萎缩有关。与白色脂肪组织隔室的缺失相关，VDR KO小鼠腺体中平滑肌肌动蛋白染色增加，表明间质微环境发生了变化。VDR小鼠乳腺组织中caspase-3的激活和Bax表达的增加表明细胞凋亡的增强可能导致导管分支的丧失。VDR KO小鼠腺体的这些形态变化与卵巢功能衰竭和血清17β-雌二醇降低有关。随着年龄的增长，VDR KO小鼠也表现出脂肪组织储存的进行性损失、低肽血症和代谢率的增加。这些发育研究表明，在正常血钙条件下，VDR信号的丢失与年龄相关的雌激素缺乏、上皮导管分支的破坏、异常的能量消耗和乳腺脂肪室的萎缩有关。
The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment.
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影响因子：
2.5
作者：
Couldrey, C;Moitra, J;Green, J
通讯作者：
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影响因子：
4.4
作者：
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作者：
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作者：
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通讯作者：
Lubahn, DB
DOI：
10.1016/j.biocel.2007.06.025
发表时间：
2007-01-01
影响因子：
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作者：
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通讯作者：
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