The role of prolactin and growth hormone in mammary gland development

The role of prolactin and growth hormone in mammary gland development
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DOI:
10.1016/s0303-7207(02)00286-1
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发表时间:
2002-11-29
影响因子:
4.1
通讯作者:
Binart, N
Binart, N
中科院分区:
医学2区
文献类型:
--
作者:
Kelly, PA;Bachelot, A;Binart, N

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乳腺的发育和分化主要发生在怀孕期间。PRL受体(PRLR)基因零突变的雌性纯合子(-/-)由于囊胚植入完全失败而不育。在黄体酮治疗的小鼠中,妊娠得以挽救,但乳腺严重发育不全。有趣的是,雌性半合子的PRLR(+/-)在第一次泌乳时几乎完全不能泌乳。这种表型。在近亲繁殖的129/Sv小鼠的第二次妊娠和随后的妊娠中消失,但在近亲繁殖的C57BL/6小鼠中保持。在GH受体(GHR) KO小鼠产仔数明显减少,可能是由于卵巢缺陷。为了评估GH和PRLR在乳腺发育中的相关性,我们将GHR和PRLR缺失的上皮移植到野生型小鼠清除的脂肪垫中。这些研究表明上皮GHR不是乳腺功能性发育所必需的。相比之下,上皮prlr是乳腺发育和妊娠期间乳蛋白基因表达所必需的。由于GHR -/-小鼠的导管发育受损,似乎GH信号通过间质室传递。综上所述,现在已经确定GH和PRL在不同的隔室中激活Stat5,反映了它们在导管和肺泡发育和分化中的特定作用。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Development and differentiation of the mammary gland occur primarily during pregnancy. Females homozygous (-/-) for the null mutation of the PRL receptor (PRLR) gene are sterile due to a complete failure of blastocysts to implant. In progesterone-treated mice pregnancy is rescued but the mammary gland is severely underdeveloped. Interestingly, females hemizygous for the PRLR (+/-) in their first lactation show an almost complete failure to lactate. This phenotype. disappears in the second and subsequent pregnancies in inbred 129/Sv mice but is maintained in inbred C57BL/6 mice. In GH receptor (GHR) KO mice litter size is markedly decreased, probably due to an ovarian defect. To assess the relevance of the GH and PRLRs in the mammary gland development, GHR and PRLR null epithelia were transplanted into cleared fat pads of wild-type mice. Such studies show that epithelial GHR is not required for functional mammary development. In contrast, epithelial PRLRs are required for mammary development and milk protein gene expression during pregnancy. Since ductal development is impaired in GHR -/- mice, it appears that GH signals through the stromal compartment. In summary, it is now established that GH and PRL activate Stat5 in separate compartments, reflecting their specific roles in ductal and alveolar development and differentiation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.