CHANGES IN SERUM CONCENTRATIONS OF CONJUGATED AND UNCONJUGATED STEROIDS IN 40-YEAR-OLD TO 80-YEAR-OLD MEN

It is well recognized that aging in men is accompanied by a decline in the serum levels of some adrenal and testicular steroids, but little or no attention has focused on the multiple steroid metabolites that a re formed by steroid-converting enzymes in target tissues. In the pres ent study, we have examined in detail the serum concentrations of a la rge series of adrenal and testicular steroids and their most significa nt metabolites produced in intracrine peripheral tissues. The serum co ncentrations of 26 conjugated and unconjugated C-21-, C-19-, and C-18- steroids were measured in 2423 men aged 40-80 yr. The serum concentra tions of the major circulating adrenal C(19-)steroids, namely dehydroe piandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta,1 7 beta-diol and its sulfate, and androstenedione, decreased by about 6 0% between the ages of 40-80 yr. The small decrease in the serum conce ntrations of progesterone and pregnenolone in the presence of increase d levels of cortisol and markedly decreased levels of DHEA, androst-5- ene-3 beta,17 beta-diol, and their polar metabolites suggests that adr enal 17,20-lyase is particularly affected by aging. In addition to a m arked decline in the serum concentrations of adrenal C(19-)steroids, a smaller, but significant, decrease occurred in serum testosterone. Ho wever, serum dihydrotestosterone levels remained constant, but the glu curonidated derivatives of dihydrotestosterone metabolites (androstane -3 alpha,17 beta-diol glucuronide, androstane-3 beta,17 beta-diol gluc uronide, and androsterone glucuronide) were reduced by 45-50%, suggest ing that 5 alpha-reductase activity in peripheral tissues may show a c ompensatory increase during aging. Analysis of the fatty acid esters o f DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly d ecrease between 40-80 yr of age, although such a decrease in DHEA-FA l evels was smaller than that in DHEA and DHEA-S, suggesting that the fo rmation of DHEA-FA may be specifically increased during aging. In summ ary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small de crease in the testis, the activity of the steroid-converting enzymes p resent in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decre ase of about 50% in total androgens in men between the ages of 40-80 y r. Such a decrease probably affects many physiological processes durin g aging.