Matsumoto Hiromichi, Zhao Xuemei, Das Sanjoy K, Hogan Brigid L M, Dey Sudhansa K
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7336, USA.
Dev Biol. 2002 May 15;245(2):280-90. doi: 10.1006/dbio.2002.0645.
Genes encoding components of the hedgehog signaling pathway are dynamically expressed in the mouse uterus preparing for implantation. Indian hedgehog (Ihh), patched (Ptc), and Gli3 are expressed at low levels in the endometrial epithelium on day 1 of pregnancy. Transcription of Ihh increases dramatically in the luminal epithelium and glands from day 3, reaching very high levels on day 4. Over the same period, Ptc, Gli1, Gli2, and noggin are strongly upregulated in the underlying mesenchymal stroma. Transcription of Ihh in ovariectomized mice is induced by progesterone but not by estrogen. Lower induction of Ihh, Ptc, and Hoxa10 is seen in response to progesterone in the uteri of Pgr(-/-) mutant mice lacking progesterone nuclear steroid receptor. This finding suggests that the hormone may regulate Ihh through both nuclear receptor-dependent and -independent pathways. We describe a method for culturing uterine explants in the absence of epithelium. Under these conditions, recombinant N-SHH protein promotes the proliferation of mesenchyme cells and the expression of noggin. We propose that IHH made by the epithelium normally functions as a paracrine growth factor for stromal cells during the early stages of pregnancy.
编码刺猬信号通路成分的基因在准备着床的小鼠子宫中动态表达。妊娠第1天，印度刺猬因子（Ihh）、patched（Ptc）和Gli3在子宫内膜上皮中低水平表达。从第3天开始，Ihh在腔上皮和腺体中的转录显著增加，在第4天达到非常高的水平。在同一时期，Ptc、Gli1、Gli2和头蛋白在下方的间充质基质中强烈上调。去卵巢小鼠中Ihh的转录由孕酮诱导，但不由雌激素诱导。在缺乏孕酮核类固醇受体的Pgr(-/-)突变小鼠的子宫中，对孕酮的反应中Ihh、Ptc和Hoxa10的诱导较低。这一发现表明，该激素可能通过核受体依赖性和非依赖性途径调节Ihh。我们描述了一种在无上皮条件下培养子宫外植体的方法。在这些条件下，重组N-SHH蛋白促进间充质细胞的增殖和头蛋白的表达。我们提出，上皮产生的IHH在妊娠早期通常作为基质细胞的旁分泌生长因子发挥作用。
