STEROID HORMONES AND AGING IN MAN 419 



neither the loci of transformations nor the enzymatic systems for which 

 the steroidal products act as substrates are known. Finally, when it 

 comes to possible age-related influences on even known enzyme sys- 

 tems, we are quite in the dark. Do we deal with alterations in the syn- 

 thesis of these enzymes, or in the synthesis of their co-factors, or in the 

 accumulation of their inhibitors? 



For certain important steroidal products we lack any data on their 

 variations in relation to age. W^ith respect to the adrenocortical prod- 

 ucts perhaps our greatest deficiency is lack of such knowledge con- 

 cerning the "life-maintaining" hormone, aldosterone. Another signifi- 

 cant corticosteroid is corticosterone. Other adrenocortical products may 

 loom large in old age. For example, if the decline in 17-ketosteroid out- 

 put is limited by the reduced rate of transformation of 17a-hydroxy- 

 pregnenolone to dehydroisoandrosterone, then the former may be 

 present in relative excess in the blood of aged individuals. What would 

 be the biological consequences of such an excess? Are there possible 

 effects of such a compound on connective tissue, on ground substance, 

 on fibroblastic phenomena, and so on? 



The decline in ll-deoxy-17-ketosteroid preciu'sor with advancing 

 age may not be the sole expression of age-affected metabolism of this 

 class of compound. For instance, the possible non-ketonic metabolites 

 have not been examined in relation to age. Among them may be com- 

 pounds having significant physiological effects. Similar considerations 

 apply to estrogen metabolites. Actually estrone, estradiol, and estriol 

 are the three thus far most easily measured estrogens in human urine, 

 but seven more metabolites have been identified in recent years ( Mar- 

 rian, 1958; Fishman and Gallagher, 1958). How their production and 

 turno\'er may be related to aging is unknown. That any of them may 

 play a role in involutionary processes must be examined as a possibility. 



In this paper we have considered only the relationships of steroid 

 biosynthesis and metabolism to aging. We cannot in the time available 

 inquire into the physiological actions of these substances in aging tar- 

 get tissues. The pervasive role of the steroid hormones as regulators of 

 a vast complex of bodily processes daily becomes more and more evi- 

 dent. Both the normal and the pathological activities of practically 

 e\'ery organ of the body are to a greater or lesser degree affected by 

 endogenous steroid. Nhmy of the most evident symptoms of "normal" 

 aging— such as muscle wastage, connective tissue changes, greater or 

 lesser degrees of osteoporosis, and atherosclerosis— are the result of 

 processes shown to be steroid-affected. Even the well-guarded central 

 nervous system has been found to respond to steroidal hormone action. 

 And when one considers the degeneratixe diseases, time and again 

 evidence emerges that their course may be altered by steroid action. 

 If a degree of prophecy may be allowed, we would state that in a 

 not-too-distant day comprehension of the production, metabolism, and 



