Adlercreutz H, Martin F, Pulkkinen M, Dencker H, Rimér U, Sjöberg N O, Tikkanen M J
J Clin Endocrinol Metab. 1976 Sep;43(3):497-505. doi: 10.1210/jcem-43-3-497.
Estrogen metabolism in the human intestine was studied in two ways. Firstly, by measuring the excretion of 12 estrogens in pooled human late pregnancy feces before and during the administration of ampicillin (2 g/day). Secondly, by administering 5.4 and 20 mg of 16alpha-hydroxyestrone orally to two postmenopausal women and analyzing the estrogens in simultaneously drawn portal and peripheral venous blood samples at time intervals from 0 to 150 min after steroid administration. The majority of the estrogens in normal pregnancy feces were unconjugated. The amounts of estradiol, estreon and 16-epiestriol excreted, relative to the principal estrogen estriol, were greater than in pregnancy bile or urine and 16alpha-hydroxyestrone, an important biliary estrogen, was only present in trace amounts. Considerable quantities of 15alpha-hydroxyestradiol-17beta were also found. Ampicillin administration, which decreases intestinal bacterial steroid metabolism, caused a huge increase in the fecal excretion of conjugated estrogens. In particular it caused very striking increases in the excretion of both unconjugated and conjugated, estriol, 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol and 2-methoxyestrone. These findings emphasize the active role played by the intestinal microflora in estrogen metabolism under normal conditions. Administration of 16alpha-hydroxyestrone resulted in increases in portal venous unconjugated and conjugated 16alpha-hydroxyestrone, 16-oxoestradiol-17beta, 15alpha-hydroxyestrone, 16-epiestriol and conjugated estriol levels. The most significant finding in both subjects was the large increase in portal venous unconjugated 15alpha-hydroxyestrone. This would suggest that the human intestine (or intestinal contents) has the ability to carry out the transformation, 16alpha-hydroxyestrone leads to 15alpha-hydroxyestrone. Increases in the same estrogens were found in peripheral plasma, with the increase in conjugated estriol occurring in peripheral blood before it was seen in portal blood. The largest elevations in peripheral plasma values were seen in unconjugated estriol and conjugated 16alpha-hydroxyestrone in the subject who received the 20 mg dose and in unconjugated 16alpha-hydroxyestrone and 16-oxoestradiol-17beta in the subject who had the 5.4 mg dose. The intestinal and enterohepatic metabolism of estrogens is discussed in relation to these findings.
对人体肠道中的雌激素代谢进行了两种方式的研究。其一，通过测量在服用氨苄西林（2克/天）之前及期间收集的人类妊娠晚期粪便中12种雌激素的排泄量。其二，给两名绝经后女性口服5.4毫克和20毫克的16α-羟基雌酮，并在给予类固醇后0至150分钟的时间间隔内，分析同时采集的门静脉和外周静脉血样中的雌激素。正常妊娠粪便中的大多数雌激素是未结合的。相对于主要雌激素雌三醇，排泄出的雌二醇、雌酮和16-表雌三醇的量，比妊娠胆汁或尿液中的量更大，而重要的胆汁雌激素16α-羟基雌酮仅以痕量存在。还发现了相当数量的15α-羟基雌二醇-17β。服用氨苄西林会减少肠道细菌的类固醇代谢，导致结合雌激素的粪便排泄量大幅增加。特别是，它导致未结合和结合的雌三醇、15α-羟基雌酮、15α-羟基雌二醇和2-甲氧基雌酮的排泄量都有非常显著的增加。这些发现强调了在正常情况下肠道微生物群在雌激素代谢中所起的积极作用。给予16α-羟基雌酮导致门静脉未结合和结合的16α-羟基雌酮、16-氧代雌二醇-17β、15α-羟基雌酮、16-表雌三醇和结合雌三醇水平升高。在两名受试者中最显著的发现是门静脉未结合的15α-羟基雌酮大幅增加。这表明人体肠道（或肠道内容物）有能力进行16α-羟基雌酮向15α-羟基雌酮的转化。外周血浆中也发现了相同雌激素的增加，结合雌三醇在外周血中的增加先于门静脉血。在接受20毫克剂量的受试者中，外周血浆中未结合雌三醇和结合16α-羟基雌酮的升高幅度最大；在接受5.4毫克剂量的受试者中，外周血浆中未结合16α-羟基雌酮和16-氧代雌二醇-17β的升高幅度最大。结合这些发现对雌激素的肠道和肠肝代谢进行了讨论。
