STEROID HORMONES AND AGING IN MAN 



409 



rectly from cholesterol by side-chain scission between carbons 17 and 

 20, or from 17-hydroxy-A^-pregnenolone by similar scission in this 

 molecule between carbons 17 and 20 (see Figure 1). Another 11-deoxy- 

 17-ketosteroid found in adrenal vein blood is A^-androstenedione. This 

 may arise from dehydroisoandrosterone by the action of a 3f3-o\ de- 

 hydrogenase or from 17-hydroxyprogesterone by desmolase action be- 

 tween carbons 17 and 20. We have pointed out (Pincus, 1960) that the 

 age-impaired enzyme system activity is probably not the 3/:^-ol-dehydro- 

 genase since apparently it operates at an undiminished rate in produc- 

 ing corticosteroids from A^-pregnenolone. Of course there may be a 

 dehydrogenase specific for dehydroisoandrosterone, but none has thus 

 far been demonstrated. The age-conditioned bottleneck would there- 

 fore appear to be either the 17-20-desmolase system acting on choleste- 

 rol or that acting on 17-hydroxy-A^-pregnenolone (and probably also 

 on 17-hydroxyprogesterone). The latter, at the moment, seems the 

 most likelv, since our efforts to obtain labeled dehvdroisoandrosterone 



CHOLESTEROL 



a'- PREGNENOLONE 



1 7*- OH - a'- PREGNENOLONE 



DEHYDROISOANDROST ERONE 



I7<x- OH- PROGESTERONE 



A -ANOROSTENEDIONE 



Figure 1. The biosynthesis of adrenal androgens. 



