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SUMMARY
The α-ketolic steroid R6, previously described by de Courcy, Bush, Gray & Lunnon [1953], has been identified as tetrahydrocorticosterone. The structures of X6 and some other αβ-unsaturated ketones appearing on chromatograms of urine extracts and giving the Bush soda fluorescence reaction are discussed. Four of these compounds are of exogenous origin and follow the ingestion of citrus fruits.
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SUMMARY
The two α-ketolic steroids R3 and R4, previously described by de Courcy, Bush, Gray & Lunnon [1953], and which lack the Δ4-3-keto group, have been identified as tetrahydrocortisol (5β-pregnane-3α:11β:17α:21-tetrol-20-one) and tetrahydrocortisone (5β-pregnane-3α:17α:21-triol-11:20 dione). The Δ4-3-ketone, X3, is shown to be identical with Reichstein's compound E (Δ4-pregnene-11β:17α:20β21-tetrol-3-one). X4 has chromatographic properties resembling Reichstein's compound U (Δ4-pregnene-17α:20β:21-triol-3:11-dione).
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SUMMARY
The steroids excreted by patients receiving oral prednisone and oral prednisolone have been investigated. The two compounds present in largest amount were isolated and identified as prednisone and prednisolone. Present in smaller amounts were the corresponding 20β-alcohols. A fifth compound had properties suggestive of pregna-1:4-dien-17α:20α:21-triol-3:11-dione. There is no evidence that prednisone and prednisolone are converted in the body to cortisol, cortisone, or their derivatives, and the investigations suggest that prednisone is metabolized in part by reduction of its 11-ketone group to a 11-hydroxy group and prednisolone by oxidation of its 11-OH group to an 11-ketone group. These two compounds are thus metabolically inter-convertible. Reduction of the 20-ketone group can occur in both compounds.
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SUMMARY
The binding of plasma cortisol to transcortin at 37° c was studied in normal men and in non-pregnant and pregnant women. The mean concentrations of transcortin were 8, 11·5 and 14 × 10−7 moles/l. and the percentages of the binding sites occupied by cortisol were 45, 24 and 40%, respectively. The mean values of the equilibrium constants were 2·9, 1·8 and 4·6 × 107 l./mole, suggesting that there might be a qualitative difference in transcortin from the three groups. The mean concentration of diffusible cortisol was 1·12 μg./100 ml. in men and 0·65 μg./100 ml. in non-pregnant and pregnant women.
The significance of these findings is discussed.
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SUMMARY
The metabolism of [4-14C]cortisol in a patient with Cushing's syndrome has been studied by the isolation, identification and measurement of the specific radioactivities of the major metabolites.
The results show that the metabolism of cortisol was not abnormal in the aspects studied. The biological half-lives of cortisol and of the tetrahydrocorticosteroid metabolites were found to be normal. Data obtained on excretion rates of metabolites indicated that the metabolic pathways of cortisol were normal. There was no evidence for an increased conversion of cortisol to 6β-hydroxycortisol when the excretion of the latter was expressed as a fraction of the cortisol production.
The overall pattern was one of an abnormally high secretion of cortisol by the adrenals, resulting in a proportionally high excretion of tetrahydrocortisone, tetrahydrocortisols, cortolones, cortols, 11-oxygenated 17-oxosteroids, 6β-hydroxycortisol, cortisone and cortisol. Apart from an increased ratio of 11β-hydroxy-metabolites to 11-oxo-metabolites, each metabolite, expressed as a fraction of the cortisol secreted, was excreted in a normal proportion.
Hence, in spite of the grossly elevated cortisol secretion rate, the major pathways available for cortisol metabolism were not overloaded and there was no evidence of increased metabolism via minor pathways.
Evidence for an increased secretion of corticosterone by the adrenals was obtained by the isolation of abnormal amounts of tetrahydrocorticosterone.
