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Isolierung und Identifizierung von 6ß-OH-Corticosteron

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Zusammenfassung

1. Aus Urinextrakten männlicher E3-Ratten wurde papierchromatographisch als Hauptmetabolit des Corticosterons ein stark polarer Metabolit isoliert.

2. Das Verhalten des Metaboliten in verschiedenen organischen Lösungsmittelsystemen bei der Papierchromatographie, die Aufnahme der UV-, H2SO4- und IR-Spektren, der molare Extinktionskoeffizient, die Schmelzpunktbestimmung sowie die Umlagerung in siedendem wäßrig-methanolischen Alkali zu Allopregnan-11ß,21-diol-3,6,20-trion sprechen dafür, daß es sich bei der aus Rattenurin isolierten Verbindung um 6ß-OH-Corticosteron handelt.

3. Nach Vorbehandlung der Ratten mit CFT 1201 — einem Hemmstoff der Lebermikrosomenenzyme — erfolgt ein signifikanter Abfall der Ausscheidung von 6ß-OH-Corticosteron. Daraus kann geschlossen werden, daß die 6ß-Hydroxylierung nicht in den Nebennieren, sondern in den Lebermikrosomen vor sich geht.

4. Die quantitative Ausscheidung von 6β-OH-Corticosteron ist bei intakten männlichen E3-Ratten im oralen Dauerinfusionsversuch in den ersten 6 Std um 35–40% höher als in den nachfolgenden 15 Std.

5. Die ausgeschiedene Menge 6β-OH-Corticosteron ist von dem Natriumgehalt der Infusionslösung abhängig; nach Gabe 0,9% iger Kochsalzlösung sind die Werte signifikant höher als nach Verabreichung 0,2% iger NaCl-Lösungen.

6. Es steht noch nicht fest, ob 6β-OH-Corticosteron biologisch inaktiv ist.

Summary

1. A strongly high polar metabolite has been isolated as the main metabolite of corticosterone out of urinary extracts of male rats.

2. Rf-values on paper chromatograms in different organic solvent systems, UV-, H2SO4- and IR-spectra, molar extinction coefficient, determination of melting point and conversion to Allopregnan-11β-21-diol-3,6,20-trione by treatment on refluxing aqueous methanolic alkali indicate this metabolite being identical with 6β-OH-Corticosteron.

3. Pretreatment of male rats with CFT 1201 — an inhibitor of enzymes of liver microsomes — is followed by a significant decrease in 6β-OH-Corticosterone excretion. This suggesting 6β-hydroxylation being performed in the microsomes of the liver and not those of the adrenal glands.

4. The urinary excretion of 6β-OH-corticosterone of male rats is 35–40% higher during first 6 hours of an oral infusion experiment with saline solution than in the following 15 hours.

5. The quantity of 6β-OH-corticosterone excreted in urine depends on the sodium concentration of the infusate: During administration of isotonic solution values are significant higher than during infusion of hypotonic saline solution.

6. 6β-OH-corticosterone is believed to be not an inactive matebolite of corticosteroid metabolism.

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  1. Aus dem Pharmakologischen Institut der Freien Universität Berlin, Germany

    H. Herken & E. Seeber

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Herken, H., Seeber, E. Isolierung und Identifizierung von 6ß-OH-Corticosteron. Naunyn - Schmiedebergs Arch 244, 442–456 (1963). https://doi.org/10.1007/BF00245079

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