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Background: Preeclampsia is associated with a quantitative imbalance between lipid peroxide and an antioxidant coproduced in the placenta. To investigate our hypothesis that 2-hydroxyestradiol 17-sulfate (2-OH-ES) is the placental antioxidant during pregnancy, we developed an assay for 2-OH-ES in urine and studied samples from women with and without preeclampsia. Methods: The detection and measurement of 2-OH-ES in the urine of pregnant women were performed by RIA using highly specific antiserum to 2-OH-ES. To confirm the reliability of the RIA method, the same samples were analyzed by HPLC using an electrochemical detector. Results: Urinary 2-OH-ES values obtained by RIA showed a close relationship to those obtained by HPLC (y = 1.1x − 0.01; r = 0.96). The urinary 2-OH-ES concentrations during the first, second, and third trimesters were 2.0 ± 0.6 (mean ± SE, n = 13), 5.3 ± 1.3 (n = 21), and 15.3 ± 2.0 μg/mg creatinine (n = 54), respectively, and <0.15 μg/mg creatinine (n = 10) at 2–24 h after delivery. The concentrations in preeclamptic women during the third trimester were significantly lower, 3.9 ± 1.9 μg/mg creatinine (mean ± SE, n = 12). Conclusions: RIA can be used to measure urinary 2-OH-ES during pregnancy. The increase in urinary 2-OH-ES during gestation, its decrease after delivery, and the lower values in preeclampsia are consistent with a role of 2-OH-ES as a placental antioxidant.

Some reports have suggested the ameliorative effects of estrogens on clinical symptoms, such as short memory, in women suffering from senile dementia-Alzheimer's type, in vivo. The action mechanism of estrogen remains to be clarified, but 1) an anti-depressive effect, 2) improvement of cerebral blood flow, 3) direct stimulation of neuron, 4) development of gliacyte and 5) suppression of apolipoprotein E have been suggested. Some mechanisms may be combined, contributing to the beneficial effects on clinical symptoms.

Abstract.2-Hydroxyestradiol 17-sulphate (2-OH E2-17-S) is a catecholized form of sulphated estrogen. In vitro studies showed that its antioxidative effect is almost equal to that of free catecholestrogens, such as 2-OH E2 or 4-OH E2 and a-tocoferol, but the existance of 2-OH E2-17-S in human serum has not yet been made clear. 2-OH E2-17-S strongly antagonizes lipid peroxidation, and so it may play an important role in pregnancy, for example as an anti-oxidant in pregnancy-induced hypertension (PIH). The serum level of 2-OH E2-17-S was measured during mid to late pregnancy by a direct radioimmunoassay (RIA) without hydrolysis. The serum levels at 28-31 weeks, 32-35 weeks and 36-40 weeks of gestation were 4.68 ±0.93 (mean ± SE), 8.38 ± 1.21 and 18.31 ± 3.41 nmol/l, respectively.The serum level in PIH cases at 36-40 weeks (4.64± 1.29 nmol/1) was significantly lower than that in normal pregnancy.The 2-OH E2-17-S level in umbilical arteries was significantly higher than that in maternal peripheral vein. These results suggest that the feto-placental unit plays an important role in catecholizing E2-17-S to 2-OH E2-17-S, which may act as an antioxidant in pregnancy.

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