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



17, and 21 -oxygenation take plaee after the conversion to 

 the Zl*-3-ketone. Analyses of urinary 17-ketosteroid excretion 

 in subjects with adrenal hyperactivity have led us to the 

 conclusion that those syndromes are due in part to imbalances 

 in the concentrations of the various biosynthetic enzymes 

 (Rubin et al., 1954; Dorfman, 1954). It is also possible to 

 discuss the variations from the young normal pattern which 

 are seen in old age in terms of the same enzyme systems. 



In old age, androsterone and 8etiocholan-3a-ol-17-one 

 excretion are decreased to about 20-30 per cent of the young 

 adult level, while ll-oxygenated-5a compounds are being 

 excreted at about 50 per cent of the younger value, and 11- 

 oxygenated-5j8 steroids at about 60 per cent. Therefore, we 

 must assume that the enzyme systems converting cholesterol, 

 acetate, or other precursors to dehydroepiandrosterone are 

 the enzyme systems functioning at the lowest level in com- 

 parison with those of young adults. This would account for 

 the low excretion of 11-desoxy C^g steroids. The conversion 

 from A^-S^-OH to J*-3-ketone and the 11 -oxygenating 

 function are less impaired and such dehydroepiandrosterone 

 as is formed is converted readily to androst-4-en-ll^-ol-3,17- 

 dione. Cgi steroids are also being formed and oxygenated at 

 C-11 relatively efficiently, as shown by excretion of two-thirds 

 of the normal young adult amount of ll-oxygenated-5^- 

 steroids. 



The connection between the indicated changes in production 

 of individual adrenal hormones and the signs and symptoms 

 of old age has not yet been established. To this end, a study 

 has been started at the Worcester Foundation, in collabora- 

 tion with Dr. Eric Bloch and with Dr. Harry Freeman and 

 the research staff of the Worcester State Hospital, in which 

 twelve elderly men are to be given, for many months, steroids 

 calculated to restore the urinary a-17-ketosteroid pattern to 

 that seen in young men. Concurrently, ])eriodic tests are 

 made of recent memory, as an index of mental function, and 

 of weight-lifting ability, as an index of muscle jicrformancc. 

 The daily sublingual dose of steroids consists of 30 mg. of 



