Metabolism of Pregnenolone-7 α-3H and Progesterone-4-14C inYoung and Elderly Men

Abstract

Young and elderly men excreted into the urine twice as much of the radioactive dose of progesterone-4-C14 as of pregnenolone-7[alpha]-3H. However, a minimum of 90% of the metabolites of the latter steroid was recovered from glucosiduronate and sulfate fractions, compared to 60% for those of progesterone. Elderly subjects excreted 30% less of the radioactive dose of both steroids during the 1st collection day and 20% less as extractable conjugates in the 4-day collection period. They excreted 1/4 as much 5[beta]-pregnane-3[alpha], 20[alpha]-diol (P-diol)1 per day, 0.15 mg, as young subjects, 0.6 mg, although the ratios of conversion of the dose of pregnenolone-7[alpha]-3H to P-diol to the conversion of the dose of progesterone-4-C14 to P-diol were the same, 2.5: 1, for both groups of men. By calculation of the interconversion between the 2 chemical pools from P-diol specific activities for 3H and C14, respectively, the percentage conversion of pregnenolone to progesterone was found to be 40% for both young and elderly men. Estimated from the specific activities for [DELTA] 5-P-diol recovered after solvolysis, a maximal urinary production rate of pregnenolone averaged 9 mg/day for young men, which value would be an overestimation if pregnenolone sulfate were secreted and converted to [DELTA] 5-P-diol sulfate. In either case pregnenolone is a significant source of P-diol in young men. The marked decline in P-diol excretion by elderly men seems to be correlated with a decline in the secretion of pregnenolone.