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    Gestationsalterabhängigkeit der 11ß Hydroxistereoid Dehydrogenase in der intakten Zelle in verschiedenen Organen von Ratte und Kaninchen (1998)

    Art
    Hochschulschrift
    Autor
    Kruner, Matthias
    Quelle
    Berlin, 1998 — 65 Seiten
    Kontakt
    Institut für Tierschutz, Tierverhalten und Versuchstierkunde

    Königsweg 67
    14163 Berlin
    +49 30 838 61146
    tierschutz@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Respiratory distress syndrome (RDS) is one of the most important factors in perinatal morbidity and mortality of the newborn and is due to deficiency of the pulmonary surfactant system. Alveolar surfactant synthesis in the fetal lung depends on the effect of GCS. In a study of Hundertmark et al. (1995) in organoid cultures of fetal rat lung it was demonstrated that the intracellular effect of GCS is dependent of the reductive 11 p-HSD activity. 11 p-HSD activity plays an important role not only in the lung, but also in other organs. There are investigations, indicating that prenatal GCS stimulation may lead to an essential hypertension in adults. Oxidative 1113-HSD activity of placenta and fetal kidney protects the fetal organism from GCS effects by deactivation of the GCS.In this study we want to demonstrate whether 1113-HSD activity in intact tissues is gestational age dependent.Further we have addressed two questions:1) At what time of gestational age is 1113-HSD activity sufficient enough to accelerate lung development?2) At what time of gestational age is the protection of 11 p-HSD activity in placenta and kidney sufficient enough to protect the organism from unwanted sideeffects? We examined lung, liver, kidney, colon and placenta of fetal Wistar rats and Chinchilla rabbits. The organs were minced and rinsed. For the oxidative assay the intact cells were incubated for 3 h under addition of [3H] corticosterone, the reductive assay took 1,5 h under addition of [3H] 11 - dehydrocorticosterone. The activity of 1113-HSD was quantified as turnover per time. We showed, that the endogenous activation from 11 DH-GCS to active GCS takes place towards end of gestation. Oxidative activity of placenta and kidney is at early gestation very low. This means, that exactly at that time, when GCS application to accelerate lung maturation is indicated, the protection . of the kidney is not sufficient. We conclude, possibly we have to be very cautious with GCS application during early pregnancy because of the side effects, especially the development of an essential hypertension in the later life of the descendants, because of the insufficient protection of kidney and placenta at that time.Further studies are necessary to check clinical importance.