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  • 2000-2004  (2)
  • 1
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA-protein binding experiments using high levels of either oestrogen receptor (ER)α or ERβ imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately −160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein-DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT −160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERα or ERβ, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERα-positive MCF7 cells and ERα-negative MDA-MB231 cells both contain a transcription factor which binds specifically to both the hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA-independent mechanism than classic direct interactions with dimeric oestrogen receptors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Reproduktionsmedizin 16 (2000), S. 208-215 
    ISSN: 1434-808X
    Keywords: Keywords Relaxin ; Estrous cycle ; Ovary ; Uterus ; Implantation ; Pregnancy ; Relaxin-like factor ; Schlüsselwörter Relaxin ; Zyklus ; Ovar ; Uterus ; Implantation ; Schwangerschaft ; Relaxin-like factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Peptidhormon Relaxin wurde lange Zeit fast ausschließlich mit Veränderungen an Uterus und Zervix während der späten Trächtigkeit in Verbindung gebracht. Diese bekannten Relaxinwirkungen, die Unterdrückung von spontanen Kontraktionen sowie Erweichung und Weitung des Geburtskanals, wurden in erster Linie an den Tiermodellen Schwein und Ratte untersucht, die jedoch eine ausgeprägte systemische Relaxinphysiologie mit maximalen Serumwerten im letzen Trimester der Schwangerschaft besitzen. Bei der Frau und nichthumanen Primaten erreicht allerdings das zirkulierende Relaxin nur einen Bruchteil der Relaxinkonzentrationen im Vergleich zu diesen Tiermodellen. Ebenso findet sich der maximale periphere Relaxinwert im ersten Trimester der Gravidität. Diese Verhältnisse sprechen eher für eine parakrine Situation im Ovar und Uterus, die wahrscheinlich mit Ovulation und dezidualer Veränderung des Endometriums zum Zeitpunkt der Implantation assoziert sind. Weiterhin wird Relaxin eine Funktion bei der Osmoregulation, der Herz-Kreislauf-Regulation und der Angiogenese im Uterus zugeschrieben. Neuere Untersuchungen zeigen auch, dass Relaxin einen Modellierungseffekt auf das Hautbindegewebe besitzt, und somit eröffnen sich neue Therapiemöglichkeit für Sklerodermapatienten. Schließlich konnten weitere relaxinähnliche Peptide, mit evtl. ähnlicher Funktion, im männlichen Organismus entdeckt werden. Aus den Ausführungen soll deutlich werden, dass Relaxin nicht nur ein wichtiges Hormon der Schwangerschaft ist, sondern auch ein multifunktioneller Wachstumsfaktor mit gewebemodellierenden und rekonstruktierenden Funktionen.
    Notes: Abstract The peptide hormone relaxin has long been associated with changes in the uterus and cervix related to the suppression of spontaneous contractions and the softening and widening of the birth canal. However, most of these results were obtained in animals such as the pig or the rat which have a pronounced systemic relaxin physiology with a maximum serum level in the third trimester of pregnancy. In women and monkeys circulating relaxin levels barely ever exceed a few percent of those in other species and have a maximum in early pregnancy. This early peak probably reflects a paracrine physiology in the ovary and uterus which is associated with ovulation and decidual changes in the endometrium preparatory to implantation. Relaxin also supports other local functions related to osmoregulation, heart rhythm and tonus, and angiogenesis. Furthermore, recent studies show that relaxin can remodel connective tissue in the skin and thus offers a potential therapy for scleroderma patients. Finally, recent gene cloning studies have revealed that there are other relaxin-related peptides which may also be involved in similar relaxin-like functions, for example in the male. Thus relaxin should be regarded less as a specific hormone of late pregnancy than as a broad-range growth factor specializing in tissue remodelling and reproduction.
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