Estrogen metabolism as measured in blood and urine in female rhesus monkeys

Abstract

In order to measure the interconversions of estrone (E1) and estradiol (E2) and their conversion to the 16α-hydroxylated estrogens, 16α-hydroxy estrone (16α-OHE1) and estriol (E3), we infused 11 female rhesus monkeys with [ 3H]E2 and [ 14C]E1 and measured radioactivity in the blood as E1, E2 and 16α-OHE1 ( n = 9) and in the urine as the glucuronides of E1, E2, 16α-OHE1, and E3 ( n = 11). The mean conversion of E1 to E2 as measured in blood (percent of infused E1 measured in blood as E2, [ρ] BB 1,2) was 29.2 ± 1.6% and as measured in the urine of the same animals, [ρ] BM 1,2, was 77.4 ± 5.9%. The mean conversion of E2 to E1, [ρ] BB 2,1 was 21.5 ± 1.0% and as measured in urine, [ρ] BM 2,1 was 67.7 ± 4.6%. Thus for both estrone and estradiol only 30–35% of the interconversions occurred in pools which were in equilibrium with the blood pool of these estrogens. The remaining 65–70% occurred in a pool, probably liver, in which glucuronidation occurred immediately after conversion. The conversion ratios (the ratio of the concentration in the blood of radioactivity as 16α-OHE1 to its precursor, CR Prec, 16α-OHEI) was 0.036 + 0.008 for CR E1, 16α-OHE1 and 0.0039 ± 0.0010 for CR E2, 16α-OHE1. The percentages of administered E1 excreted in the urine as the glucuronides of E1, E2, 16α-OHE1 and E3 were 20.1 ± 1.5, 1.6 ± 0.2, 0.96 ± 0.20 and 0.76 ± 0.07 respectively. The percentages of administered E2 excreted in the urine as E1, E2, 16α-OHE1 and E3 were 14.4 ± 1.0, 2.2 ± 0.3, 0.57 ± 0.05 and 0.68 ± 0.11 respectively. Thus there are minor differences in the patterns of excreted metabolites of E1 and E2. Furthermore, 16α-OHE1 and E3 are not major metabolites of E1 or E2 in the female rhesus monkey.