E. M. Richardson

URINARY ALPHA-KETOLIC STEROID METABOLITES OF CORTICAL HORMONES ADMINISTERED TO SUBJECTS WITH ADRENAL CORTICAL INSUFFICIENCY

The analysis of urinary excretory products following the administration of known compounds is one of the classical methods for the study of their metabolism. The developments inpaper chromatographic (1) and micro-analytic (2) technics and the use of glucuronidase hydrolysis (3) have considerably decreased the difficulties of investigating steroid metabolism by this method. Using these newer technics, we have studied the urinary excretion pattern of the major alpha-ketolic steroids after the administration of the six active adrenal cortical steroids to individuals with severe adrenal cortical insufficiency. We have found, as has been demonstrated for other steroids (4), that the major alpha-ketolic metabolites result from the reduction in ring A of the steroid nucleus to the 3-alpha-hydroxy pregnane derivatives (the socalled tetrahydro form) and that the hydroxyl and ketone groups on carbon atom 11 are interconvertible for corticosterone and 1 1-dehydrocorticosterone as well as for hydrocortisone and cortisone.

Urinary excretion of C-20 reduction products of corticosterone and 11-dehydrocorticosterone

Abstract Three hundred milligrams of corticosterone was ingested by a healthy man on each of 2 days, and urine was collected for 48 hr. The urine was extracted with chloroform in the presence of β-glucuronidase. Three steroids with a glycol side chain and the Δ4-3-ketone group have been separated from the urine extract. These were identified as (I) 20β,21-dihydroxy-4-pregnen-3,11-dione; (II) 11β,20β,21-trihydroxy-4-pregnen-3-one; and (III) 11β,20α,21-trihydroxy-4-pregnen-3-one. Evidence is presented indicating the presence of compound I in the urine of a woman with hypopituitarism following ingestion of 11-dehydrocorticosterone; and of the compound II in urine collected from two men during periods of adrenocorticotropin injections.

THE EFFECT OF ACTH AND PATHOLOGICAL INCREASES IN ADRENAL CORTICAL FUNCTION ON URINARY ALPHAKETOLIC STEROID METABOLITES

Previous studies ( 1 ) have shown that the specific alpha-ketolic steroid metabolites found in the urine after administration of a known alphaketolic steroid reflect, to a limited extent, the nature of the precursor. With this study as a baseline, we have determined the major urinary alphaketolic steroid metabolites found after intravenous infusion of human subjects with ACTH, and some of those found in the urine of a man with Cushings syndrome, and in that of a womanwith metastatic adrenocortical carcinoma. The results of this study and some speculations concerning the possible nature and rate of alpha-ketolic steroid secretion are presented in this paper.

The isolation of corticosterone metabolites from the urine of normal men

Abstract The isolation of pregnane-3α,11β, 21-triol-20-one (“tetrahydrocorticosterone”), allopregnane-3α, 11β, 21-triol-20-one (“allotetrahydrocorticosterone”), and Δ4-pregnene-21-ol-3,11,20-trione (“11-dehydrocorticosterone”) from urines of normal men is described. Allopregnane 3α, 21-diol-11, 20-dione (tetrahydro-11-dehydrocorticosterone) has been tentatively identified. All four compounds have previously been identified in urine extracts of individuals receiving corticotropin. A tabulation of some of the mobilities in several chromatographic systems of the “major” α-ketolic substances found in the urine of normal subjects is presented. The methods are presented in detail.