Reichstein compoundsの正常人および肝硬変患者尿中への1日排泄量について

抄録

Reichstein's compounds, C-20 reduced metabolites of cortisol, have been found in human urine after loading with exogenous cortisol or ACTH. No reports fire found at present about urinary daily excretion of these metabolites in normal subjects under basal conditions.
In this paper, by means of thin layer chromatography, the daily excretion of these compounds as well as tetrahydro- (THF + a11oTHF, THE) and hexahydrocompounds (cortols & cortolones), were determined in 5 normal subjects (male) and 6 patients with cirrhosis of the liver, before and after oral administration of 100 mg of cortisol.
Each urine specimen, after hydrolysis with β-glucuronidase, was extracted with ethyl acetate. Crude extract after washing was separated to fraction A and B by the first thin layer ', chromatography (Kieselgel GF₂54, solvent : cyclohexan-isopropanol 6 : 4). Fraction A, containing Reichstein's compounds and hexahydrocompounds, was oxidized with periodic acid and fractionated using the partition thin layer chromatography of Chang's, and finally determined by Zimmermann reaction. Fraction B was rechromatographed on another silicagel plate using solvent stystem methylene dischloride-ethanol to separate each tetrahydro-compounds, and to quantify by blue tetrazolium reaction. Recovery study was carried out using each ¹⁴C-labelled steroid. Regular existence of Reichstein's compounds in normal urine was demonstrated by preparing the autoradiogram of fraction A..
Normal urinary excretions of Reichstein's E & U in the basal state were 0.27±0.08 mg and 0.22±0.09 mg per 24 hours, respectively. The values of tetrahydro-and hexahydro-compounds in normal state were in good agreement with the data previously reported.
In patients, a three-fold increase was observed in the excretion of Reichstein's compounds as compared to normals. Cortols and cortolones also increased significantly, while tetrahydro-compounds decreased. This tendency was greater after loadimng with cortisol.
These results suggest that severe damage of the liver function would remarkably impair the metabolic pathway to tetrahydro-compounds orf cotisol since the reduction of ring-A occurs solely in the liver. And the greater excretion of C-20 reduced metabolites in the cirrhotic patients also suggests the relative predominance of the pathway via Reichstein's compounds, which is recognized as the minor route in normal cortisol metabolism.