title: Development of progestin-specific response in the chicken oviduct.
abstract: Avidin is a host acute defense protein induced by progestins and by inflammation caused by injurious factors such as microbes, viruses, toxic factors or tissue trauma. In the reproductive tract of egg-laying vertebrates avidin has evolved into a progestin-dependent secretory protein involved in anti-microbial action through its biotin avidity. For "progestin-dependent avidin" production, cellular differentiation by estrogen is necessary. In contrast, the expression of "progestin-independent or inflammation-induced avidin" does not require differentiation. Many cell types such as macrophages, heterophils and fibroblasts can produce avidin after non-specific cellular injuries. The wide distribution of avidin in avian, reptilian and amphibian species could be explained on the basis of its vital functions such as antimicrobial or antifungal, metabolic and immunomodulatory actions. The ontogeny of the progestin-dependent avidin synthesis is a complex event involving oviductal differentiation by steroid hormones leading to a specific gene expression. The first phase in oviductal differentiation by estrogens is characterized by a new chromatin organization and by an infiltration of progesterone receptor (PR)-containing mesenchymal cells into the subepithelial mucosa leading to epithelial cell differentiation ("mesenchymal and epithelial cell interaction"). The second phase in the differentiation of progestin-induced response is dependent on the presence of PR in the secretory cells. Two kinds of PR expression occur in the oviduct. The first is a "constitutive PR" and is found in the epithelial, submucosal and peritoneal cells of the immature chick oviduct without steroid treatment, and the second is an "inducible PR" found especially in the mucosal mesenchymal and smooth muscle cells. Avidin production requires PR in the target cells, but not all PR-containing cells can produce avidin. Therefore, in addition to PR, other transcription factors are needed to define the target cell specificity of the response to progestins. Earlier biochemical studies suggested that cytosolic and/or nuclear unoccupied PR was complexed as an 8 S form with the heat shock protein 90 (hsp90). Our immunohistochemical results, however, indicate that PR in vivo is not bound to hsp90, which is located entirely in the cytoplasm, whereas PR is an entirely nuclear protein in both ligand-occupied and unoccupied forms. Therefore, we assume that PR is a monomeric (4S) or homodimeric (5S) (chromatin?) protein associated to DNA. Ligand binding to PR appears to lead to a conformational change, dimer formation, tighter binding to PRE (progesterone responsive element) and to transcription factors, phosphorylation and proteolysis of PR as well as a chromatin change.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Biomedical Sciences, University of Tampere, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Tuohimaa
authors.forename: T
authors.initials: T
authors.lastname: Joensuu
authors.forename: J
authors.initials: J
authors.lastname: Isola
authors.forename: R
authors.initials: R
authors.lastname: Keinänen
authors.forename: T
authors.initials: T
authors.lastname: Kunnas
authors.forename: A
authors.initials: A
authors.lastname: Niemelä
authors.forename: A
authors.initials: A
authors.lastname: Pekki
authors.forename: M
authors.initials: M
authors.lastname: Wallén
authors.forename: T
authors.initials: T
authors.lastname: Ylikomi
authors.forename: M
authors.initials: M
authors.lastname: Kulomaa
mesh_terms: D000818:Animals; D001360:Avidin / Q000096:biosynthesis / Q000235:genetics*; D002645:Chickens / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D008957:Models, Genetic; D010057:Oviducts / Q000378:metabolism*; D011372:Progestins / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone; D001360:Avidin