THE RENAL CLEARANCE OF NEUTRAL 17-KETOSTEROIDS IN MAN*

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Abstract
INTRODUCTION APPROXIMATELY 15 to 26 per cent of the neutral 17-ketosteroids in normal human urine consists of dehydroepiandrosterone (1). The realization that, in human peripheral blood, by far the greatest portion of the neutral 17-ketosteroids occurs as dehydroepiandrosterone (2, 3) has aroused curiosity concerning the role of this compound in the intermediary metabolism of the adrenocortical steroids. The quantities of androsterone in human blood have been reported to be much smaller (3). Although it is possible that the dehydroepiandrosterone itself in human plasma is not derived primarily from the adrenal cortex (4), its preponderance in the blood has not been explained. These investigations were designed to study the renal clearance of the 17-ketosteroids in man and to determine whether renal factors might account for the high level of dehydroepiandrosterone in human blood. METHODS A normal human subject, aged 34 years, was used for most of these studies. Dehydro epiandrosterone or androsterone was administered separately in various doses by mouth; in one experiment both were administered together as the hemisuccinates by vein. Dehydroepiandrosterone acetate was administered orally in a dose of 2 Gm. dissolved in a small volume of hot ethanol, which was then rapidly diluted with a large volume of ice water immediately before use. Androsterone, free or as the hemisuccinate, was administered on several occasions by mouth in doses of 0.5 to 2.0 Gm. During each experiment large volumes of water were ingested in order to guarantee adequate volumes of urine, and several accurately timed periods of urine collection were established following administration of the steroid, at the midpoint of which specimens of blood were obtained in a heparinized syringe. The blood was centrifuged and the plasma was extracted by methods previously described (3). The extracts of both urine and plasma specimens were extracted continuously with ether at pH 1.0 for forty-eight hours. In certain instances hydrolysis was also carried out with beta-glucuronidase (beef liver) in acetate buffer (pH 4.5) and by dioxane, using the method of Cohen and Oneson (5). All residues were chromatographed on Florosil by the method of Gardner for 17-ketosteroids (6). The appropriate eluate was separated into alpha and beta fractions by digitonin precipitation (7). The alpha and beta fractions were then analyzed by various procedures: the Zimmermann reaction, according to the method of Wilson (8); the Pincus reaction (9); and the Allen method for dehydroepiandrosterone (10). Pooled fractions of blood, after the administration of either steroid by mouth, were examined by infra-red spectroscopy in order to guarantee that the residues were identical with the administered compound. The creatinine content of urine and plasma was determined by the method of Hare (11).