Steroid metabolism in essential hypertension

Dey, Arun Chandra (1974) Steroid metabolism in essential hypertension. Masters thesis, Memorial University of Newfoundland.

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Abstract

Alterations of steroid metabolism in hypertension have been investigated with male and female normal and essential hypertensive subjects. Three groups of urinary metabolites have been quantitated: 1. androsterone, etiocholanolone and dehydroepiandrosterone (11-deoxy-17-ketosteroids, C₁₉O₂-KS), 2. 11-keto and 11β-hydroxy androsterone and 11-keto and 11β-hydroxy etiocholanolone (11-oxy-17-ketosteroids, C₁₉O₃-KS), and 3. 17-ketogenic steroids (KGS) oxidised to etiocholanolone, 11β-hydroxy androsterone and 11β-hydroxy etiocholanolone. The urinary steroids were hydrolysed enzymatically, fractionated on silica gel columns and estimated as trimethyl silyl ether derivatives by gas liquid chromatography. -- The following statistically significant differences were found in the excretion of metabolites by normal and hypertensive subjects. -- 1. C₁₉O₂-17KS fraction: the excretion of etiocholanolone glucuronide and dehydroepiandrosterone sulfate was markedly reduced in the hypertensive group (P 0.001), and the ratio of the 5α/5β-reduced metabolites was higher (P 0.001). The latter suggested a relative deficiency of 5β-reductase activity in the hypertensive group. -- 2. C₁₉O₃-17KS fraction: the excretion of the 5α-reduced metabolites was higher (P 0.01) in the hypertensive group, and the 5α/5β ratio was also increased (P 0.01), due to the increased 5α-compounds. No significant reduction was found for the 5β-reduced metabolites. -- 3. KGS fraction: the excretion of both 5α- and 5β- reduced compounds was higher (P 0.05) in the hypertensive group, but the 5β-compounds predominated in both normal and hypertensive groups. An increased excretion of 5β-reduced metabolites may suggest that the 5β-reductase activity is more active in the metabolism of the 17-ketogenic steroids than C₁₉O₂-17KS. -- The influence of the "11-oxy" function and corticosteroid "Side chain" on the relative 5α- and 5β- reductase enzyme activities and the influence of blood pressure has been discussed. -- Comparison of the proportions of reduced metabolites in the urine of normal and essential hypertensive subjects indicates that they are relatively unaffected by age, sex or intensity of blood pressure.

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