title: Indian hedgehog as a progesterone-responsive factor mediating epithelial-mesenchymal interactions in the mouse uterus.
abstract: 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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7336, USA.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhao
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
authors.forename: Brigid L M
authors.initials: BL
authors.lastname: Hogan
authors.forename: Sudhansa K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010052:Ovariectomy; D019899:Paracrine Communication / Q000187:drug effects; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D004967:Estrogens; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011374:Progesterone; D011506:Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000099176:Noggin Protein; C498520:Gli1 protein, mouse; C000606240:Ptch1 protein, mouse