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A reliable radio-ligand assay has been developed for the measurement of 17-hydroxypregnenolone in human peripheral vein plasma. The mean plasma concentration of 17-hydroxypregnenolone was, in men, 1.9 mmug/ml; and in women, 3.5 mmug/ml. These means were not significantly different from each other, and the levels were the same in the follicular and luteal phases of the menstrual cycle. In women, the adrenal cortex was the source of the 17-hydroxypregnenolone; in men, 40% was produced by the testis. Since the metabolic clearance rate was about 2000 liters/24 hr production rate estimates were 4-7 mg/24 hr. The conversion of blood 17-hydroxypregnenolone to blood 17-hydroxyprogesterone and dehydroepiandrosterone was measured. This varied from 5 to 20%. Thus, in women during the follicular phase, 17-hydroxyprogesterone derived from blood 17-hydroxypregnenolone could be the major fraction of the 17-hydroxyprogesterone production rate. Blood 17-hydroxypregnenolone is a minor precursor of blood dehydroepiandrosterone.

Megestrol acetate is metabolized by homogenates of rat adrenal glands to three more polar metabolites Y(2), Y(3) and Y(4). Their structures were investigated by microchemical reactions, paper chromatography, and ultraviolet and infrared spectroscopy. Metabolite Y(3) was identified as 17alpha-acetoxy-11beta-hydroxy-6-methyl-pregna-4,6-diene-3,20-dione, its oxidation product being identical with authentic 17alpha-acetoxy-6-methylpregna-4,6-diene-3,11,20-trione. It is suggested that metabolite Y(2) is 17,18-dihydroxy-6-methylpregna-4,6-diene-3,20-dione and that it also exists in the form of an alpha-ketol formed between the 18-hydroxyl and 20-oxo groups. Metabolite Y(4) is probably a tautomeric form of metabolite Y(2) as they were partially interconverted on chromatography and also have similar properties.