Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis
Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis
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DOI：
10.1016/j.ydbio.2003.11.018
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发表时间：
2004-03-15
影响因子：
2.7
通讯作者：
Shen, MM
中科院分区：
文献类型：
--
作者：
Berman, DM;Desai, N;Shen, MM
先前的研究表明，Hedgehog(HH)信号通路在许多内皮源性组织的发育和模式形成中起着关键作用。我们通过检测Sonic Hedgehog(Shh)突变胎儿的泌尿生殖表型，研究了Shh在前列腺形成中的作用。与早期报道Shh在前列腺诱导中起重要作用的工作一致，我们发现Shh突变的胎儿表现出异常的泌尿生殖系统发育，并无法形成前列腺芽。然而，出乎意料的是，我们发现这种前列腺缺陷可以通过三种不同的方法来挽救：肾移植，在雄激素存在的情况下进行外植体培养，以及给怀孕的小鼠注射双氢睾酮(DHT)，这表明Shh突变的前列腺缺陷是由于雄激素水平不足造成的。此外，我们发现环丙胺对HH信号通路的抑制并没有阻止外植体培养中的前列腺形成，而是产生了与HH信号在导管模式中的作用相一致的形态缺陷。综上所述，我们的研究表明，前列腺最初的器官发生独立于Shh进行，但Shh或其他M配体可能在随后形成前列腺模式的事件中发挥作用。(C)2003 Elsevier Inc.保留所有权利。
Previous studies have demonstrated that the Hedgehog (Hh) signaling pathway plays a critical role in the development and patterning of many endodermally derived tissues. We have investigated the role of Sonic hedgehog (Shh) in formation of the prostate gland by examining the urogenital phenotype of Shh mutant fetuses. Consistent with earlier work reporting an essential role for Shh in prostate induction, we have found that Shh mutant fetuses display abnormal urogenital development and fail to form prostate buds. Unexpectedly, however, we have discovered that this prostate defect could be rescued by three different methods: renal grafting, explant culture in the presence of androgens, and administration of dihydrotestosterone (DHT) to pregnant mice, indicating that the prostate defect in Shh mutants is due to insufficient levels of androgens. Furthermore, we find that the inhibition of Hh pathway signaling by treatment with cyclopamine does not block prostate formation in explant culture, but instead produces morphological defects consistent with a role for Hh signaling in ductal patterning. Taken together, our studies indicate that the initial organogenesis of the prostate proceeds independently of Shh, but that Shh or other M ligands may play a role in subsequent events that pattern the prostate. (C) 2003 Elsevier Inc. All rights reserved.