408 CELLS, TISSUES, AND ORGANISMS 



only slightly reduced in elderly subjects, and when the output is ex- 

 pressed per gram of creatinine, no significant age-related decline can 

 be established. 



3. For all ages, the ratio of the reduced a-ketol metabolites of Cor- 

 tisol— THE: THF:ATHF-is on the average 52:29:19, and significant 

 departures from this ratio do not occur in young men and women or in 

 older men and women. 



4. Similarly, the proportion of /:^-cortolone excreted is remarkably 

 constant in all the age groups studied, is equal to approximately 20 per 

 cent of the a-ketol total, and is highly correlated (r = 0.92) with the 

 output of THE, its closest a-ketol analogue. 



From these findings it was concluded that neither the rate of pro- 

 duction nor the rate of metabolism of the major corticosteroid, Cortisol, 

 was markedly different in younger and older subjects. This seemed to 

 be borne out by the finding that the excretion patterns of cortisone, 

 Cortisol, and their a-ketol metabolites did not differ in younger and 

 elderly subjects either preceding or following ACTH administration 

 ( Romanoff cf ah, 1957 ) . Also, the administration of Cortisol to elderly 

 subjects did not lead to any marked alteration in the urinary ratio of 

 5a ( alio ) to 5^ ( normal ) metabolites ( Pincus et al., 1955 ) . 



Consideration of urinary 17-ketosteroid output data led to different 

 findings: (1) the total 17-ketosteroid excretion, somewhat higher in 

 males, declines regularly with advancing age, and is not creatinine- 

 conditioned; (2) this decline is accountable to the marked age-related 

 decrement of ll-deoxy-17-ketosteroids, since the output of 11-oxy- 

 genated 17-ketosteroids is only slightly diminished in elderly subjects; 

 (3) the excretion of the biologically active ketonic androgens tends to 

 diminish with adxancing age at a rate comparable to that observed for 

 the ll-deoxy-17-ketosteroids, which is to be expected, since andro- 

 sterone, by far the most active urinary androgen, accounts for approxi- 

 mately 50 per cent of the ll-deoxy-17-ketosteroids in urine; (4) the 

 quantitative yield of the metabolites of testosterone administered to 

 elderly men did not differ from that obtained from younger men, but 

 a tendency for older men to excrete somewhat greater proportions of 

 5a metabolites was observed. 



From these data it was concluded that the major age-related de- 

 fect in neutral steroid production was that of the urinary ll-deoxy-17- 

 ketosteroid precursor(s). Since similar rates of decrement were seen in 

 both sexes, there are involved adrenocortical precursor(s), presumably 

 produced side-by-side with the corticosteroid precursors not markedly 

 age-conditioned. Recent data suggest that the major adrenocortical 

 precursor of the urinary 17-ketosteroids may be dehydroisoandrosterone 

 (Vander Wiele and Lieberman, 1960). Dehydroisoandrosterone may 

 be synthesized in the adrenal cortex by either of two pathways: di- 



