Longcope C, Hoberg L
Department of Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester 01655.
J Steroid Biochem. 1990 Apr;35(5):601-5. doi: 10.1016/0022-4731(90)90204-6.
In order to measure the interconversions of estrone (E1) and estradiol (E2) and their conversion to the 16 alpha-hydroxylated estrogens, 16 alpha-hydroxy estrone (16 alpha-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 16 alpha-OHE1 (n = 9) and in the urine as the glucuronides of E1, E2, 16 alpha-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, [rho]1.2BB) was 29.2 +/- 1.6% and as measured in the urine of the same animals, [rho]1.2BM, was 77.4 +/- 5.9%. The mean conversion of E2 to E1, [rho]2.1BB was 21.5 +/- 1.0% and as measured in urine, [rho]2.1BM 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 16 alpha-OHE1 to its precursor, CRPrec,16 alpha-OHE1) was 0.036 +/- 0.008 for CRE1,16 alpha-OHE1 and 0.0039 +/- 0.0010 for CRE2,16 alpha-OHE1. The percentages of administered E1 excreted in the urine as the glucuronides of E1, E2, 16 alpha-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, 16 alpha-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, 16 alpha-OHE1 and E3 are not major metabolites of E1 or E2 in the female rhesus monkey.
为了测量雌酮(E1)和雌二醇(E2)的相互转化以及它们向16α-羟基化雌激素、16α-羟基雌酮(16α-OHE1)和雌三醇(E3)的转化,我们给11只雌性恒河猴输注了[3H]E2和[14C]E1,并测量了血液中作为E1、E2和16α-OHE1的放射性(n = 9)以及尿液中作为E1、E2、16α-OHE1和E3的葡糖醛酸苷的放射性(n = 11)。在血液中测得的E1向E2的平均转化率(输注的E1在血液中以E2形式测得的百分比,[rho]1.2BB)为29.2±1.6%,在同一动物的尿液中测得的转化率([rho]1.2BM)为77.4±5.9%。E2向E1的平均转化率,[rho]2.1BB为21.5±1.0%,在尿液中测得的转化率([rho]2.1BM)为67.7±4.6%。因此,对于雌酮和雌二醇,只有30 - 35%的相互转化发生在与这些雌激素的血液池处于平衡状态的池中。其余65 - 70%发生在一个可能是肝脏的池中,在这个池中转化后立即发生葡糖醛酸化。转化比率(血液中作为16α-OHE1的放射性浓度与其前体的比率,CRPrec,16α-OHE1)对于CRE1,16α-OHE1为0.036±0.008,对于CRE2,16α-OHE1为0.0039±0.0010。作为E1、E2、16α-OHE1和E3的葡糖醛酸苷排泄到尿液中的给药E1的百分比分别为20.1±1.5、1.6±0.2、0.96±0.20和0.76±0.07。作为E1、E2、16α-OHE1和E3排泄到尿液中的给药E2的百分比分别为14.4±1.0、2.2±0.3、0.57±0.05和0.68±0.11。因此,E1和E2排泄代谢物的模式存在微小差异。此外,在雌性恒河猴中,16α-OHE1和E3不是E1或E2的主要代谢物。