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

Worcester Foundation for Experimental Bioloy Shrewsbury, Massachusetts 01545

Young and elderly men excreted into the urine twice as much of the radioactive dose of progesterone-4¹⁴C as of pregnenolone-7-³H. 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 first collection day and 20% less as extractable conjugates in the 4-day collection period. They excreted as much 5β-pregnane-3,20-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-7-³H to P-diol to the conversion of the dose of progesterone-4¹⁴-C 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 ¹⁴C, 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 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 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.

This study was supported by Grant AM-06294 from the USPHS

Received November 22, 1965.

Accepted July 7, 1966.