STUDIES IN STEROID METABOLISM. XIX. THE a-KETOSTEROID EXCRETION PATTERN IN NORMAL MALES 1

Abstract

The urinary steroids afford a means for evaluation of the production of steroid hormones by the adrenal and gonads. Any alteration in either rate of type of hormone production by the glands resulting from specific disease or from hormonal therapy therefore must be manifest by qualitative or quantitative change in the excretion of steroid hormone metabolites. In order to delineate the composition of these metabolites in normal healthy subjects, the present investigation describing the a-ketosteroid excretion pattern was undertaken. MATERIALS AND METHODSTwenty normal males, ranging in age from 21 to 76, were studied. Of this number, eighteen were White and one was Negro; Subject D31 was a Nisei. Subjects C21 and M21 were normal males hospitalized at the Peter Bent Brigham Hospital, Boston, Massachusetts, for the purpose of studying some of the metabolic effects of oral Cortisone and intravenous ACTH; Subjects K31, R32, R63, C64, M65, and M72 were subjects of similar study at the Baltimore City Hospitals, Baltimore, Maryland. Only control periods of these eight subjects are reported here. The remainder of the subjects are, or were, employees of this Institute, working and in apparent good health. The details of urine collection and handling in this laboratory have been reported previously (1).

Studies in Steroid Metabolism. XXVI. Steroid Isolation Studies in Human Leukemia

“…All urine collections were short term (5 to 16 days) except for that of subject M45 (195 days). The urinary steroid conjugates were hydrolyzed immediately after collection, by a combination of methods employing enzymatic (beef liver fi-glucuronidase), cold and/or hot acid hydrolysis (Methods A, B, C, or D [22]). …”

“…Alumina and/or magnesium silicate columns were employed in certain fractionations. Individual steroid fractions were identified by infrared spectrometry and quantitated by the modified Zimmermann reaction.The further details of the analytical procedures employed in these studies have already been described elsewhere (19,22). Variable proportions of 3a, ll,-dihydroxyandrostane-17-one and 3a, llB-dihydroxyetiocholane-17-one appeared as the A9 (11)-analogs after vigorous acid hydrolysis.…”

“…We have applied, to the study of this problem, the precise methods of isolation, identification, and quantitation of individual urinary steroids developed within the past decade (19)(20)(21)(22)(23). The detailed ketosteroid patterns of six subjects with chronic lymphatic leukemia during control periods and of one subject with acute myelogenous leukemia during a control interval and while on ACTH therapy are reported.…”

Study of the Genetic and Extra-Genetic Determinants of Alpha-Ketosteroid Production in Man

“…It is evident, therefore, that two of these triplets exhibited a striking similarity, during all of the periods studied, not only in steroid excretion, but also in the rate and pattern of biosynthesis of steroid hormones, the release of these substances into the blood stream, and the enzymatically-determined structural transformations of these hormones to the metabolites isolated and measured. In view of the individuality of these patterns in normal men (1), the variable adrenal response to ACTH by different men (16), and the established monovular origin of the triplets, the striking similarity of the steroid patterns of F and J in all periods could not be attributed to chance. These data, therefore, may be considered to demonstrate the existence of an important genetic determinant of the characteristic pattern of steroid hormone production and metabolism in man.…”

“…Qualitative and quantitative ketosteroid patterns were determined in all periods by the methods of steroid fractionation previously described (1,2). Briefly, these methods include sequential and separate hydrolysis of steroid conjugates with 3-glucuronidase and mild acid treatment, preparation of neutral fractions from ethereal extracts of the hydrolysates, fractionation of neutral extracts into "ketonic" and "nonketonic," and "a-" and "p-ketosteroid" subfractions, and isolation of individual a-ketosteroids by quantitative paper chromatography with steroid identification by infrared spectrometry when necessary.…”