416 



CELLS, TISSUES, AXD 



TETRAHYDROCORTISONE 

 (THE) 



TETRAHYDROCORTISOL 

 (THF) 



ALLOTETRAHYOROCORTISOL 

 (ATHF) 



Figure 3. Some extra-adrenal catabolites of Cortisol. 



appear to be derived by the series of transformations indicated in Fig- 

 ure 3. The ll/?-ol-dehydrogenase concerned with step 1 appears to be 

 less active in older people, and the 5a-reductase ( step 4 ) is somewhat 

 more active. With aging, then, either the concentration of these cata- 

 bolizing enzyme systems is altered or inhibitors (or accelerators) of 

 their activity are increased ( or decreased ) . The essential co-factors for 

 some of these enzyme systems have been determined, but whether they 

 are age-limited or whether specific endogenous inhibitors ( or accelera- 

 tors ) exist is not known. 



We have already discussed the probable age-limited biosynthetic 

 step in ll-deoxy-17-ketosteroid production. Quantitatively this is per- 

 haps the most striking diminishment of an intra-adrenal enzyme-system 

 activity. Again, aging may accomplish this by decreased enzyme syn- 

 thesis, by decreased availability of an accelerator or co-factor, or by 

 increased concentration in the steroidogenic tissue of a specific in- 

 hibitor. ACTH administration may increase 17-ketosteroid excretion in 

 elderly men (Pincus, 1950), so its production would not appear to be 

 limiting. However, a detailed study of individual metabolic sequences 

 after ACTH administration still needs doing. 



As indicated in Table \T, the catabolic transformations leading to 



