Induction of tryptophan oxygenase and tyrosine aminotransferase by metabolites of hydrocortisone.
Metabolites of hydrocortisone were isolated from rat liver on a preparative scale, fractionated by column chromatography on Sephadex Lh-20 and silica gel and tested for biological activity. Apart from the well known neutral metabolites, steroid glucuronides and sulfates, we obtained metabolite fractions containing non-conjugated steroidal carboxy acids and acid metabolites of unknown structure. One of these fractions induced tyrosine aminotransferase (EC 2.6.1.5) in adrenalectomized female rats but not tryptophan oxygenase (EC 1.13.11.11), whereas another one mainly increased activity of tryptophan oxygenase. The doses necessary to significantly induce both enzymes were much lower in case of these metabolites than in the case of hydrocortisone itself. The active fractions eluting from silica gel column were analyzed by thin-layer chromatography in two different solvent systems. Absence of hydrocortisone in these fractions could be clearly demonstrated. Furthermore, the active fractions eluting from the silica gel column were characterized by treatment with an extract from Helix pomatia and/or diazomethane and subsequent analysis by thin-layer chromatography. We conclude, considering the biological activity of some synthesized derivatives of hydrocortisone, that the biologically active components are acid metabolites of hydrocortisone which are not identical to any of the known metabolites.
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001711:Biotransformation; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008099:Liver / Q000378:metabolism; D051381:Rats; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase; D006854:Hydrocortisone