128 Betty L. Rubin, R. I. Dorfman and G. Pincus 



precursors, sucli as acetate, first are converted to androst-5- 

 en-3j8-ol-17-one (dehydroepiandrosterone), a Cjg steroid, and 

 pregn-5-en-3j8-ol-20-one, a C21 steroid, both still having the 

 3jS-hydroxy-z]^ structure. These are then oxidized to the 

 corresponding Zl*-3-ketones, such as androst-4-ene-3,17-dione 

 and pregn-4-ene-3,20-dione (progesterone). Oxygenation at 

 carbons 11, 17, and 21 takes place after the oxidation of ring 

 A, giving rise to androst-4-en-llj3-ol-3,17-dione in the C^g 

 series, and in the C21 series through six compounds containing, 

 in various combinations, one or two more hydroxyl groups 

 than progesterone, to the tri-hydroxy steroid pregn-4-ene-llj8, 

 17a,21-triol-3,20-dione (Cortisol). Among the compounds 

 intermediate between progesterone and Cortisol, those which 

 can contribute to the urinary 17-ketosteroids are pregn-4-en- 

 17a-ol-3,20-dione (17-hydroxyprogesterone), pregn-4-ene-llj8, 

 17a-diol-3,20-dione, and pregn-4-ene-17a,21-diol-3,20-dione 

 ( 1 1 -desoxy Cortisol) . 



Fig. 2 shows the relationships between these steroids and 

 the urinary 17-ketosteroids. Androsterone and aetiocholan- 

 3a-ol-17-one excretion reflect the adrenal production of the 

 C19O2 steroids, androst-4-ene-3,17-dione and dehydroepi- 

 androsterone (and in the male, testosterone produced by the 

 gonads), with a minor contribution from C21O4 steroids, such 

 as 11-desoxycortisol. An indication of the production 

 by the adrenal of C19O3 steroids, such as androst-4-en-llj8- 

 ol-3,17-dione, can be obtained from the urinary excretion of 

 11 -oxygenated steroids having the 5a (or androstane) con- 

 figuration, while excretion of 11 -oxygenated 5p steroids 

 (aetiocholane configuration) may be regarded as an index of 

 production of C21O5 steroids, the major one being Cortisol. 



The quantitative method used at the Worcester Foundation 

 for analysing urine extracts may be briefly described. 

 Urines were collected as twenty-four hour specimens and 

 hydrolyzed by boiling for eight minutes with 15 volumes per- 

 cent of hydrochloric acid. They were then extracted with 

 ether and fractionated according to the method of Pincus 

 (1945). After separation with the Girard reagent (Girard 



