A B S T R A C T Estriol, estriol sulfate, progesterone, and 17 neutral steroid sulfates, including estriol precursors and progesterone metabolites, were determined in 27 cord plasma samples collected after pregnancies complicated by intrahepatic cholestasis of the mother. The levels of these steroids were compared with those in the cord plasma of 42 healthy controls.In the cord plasma, the steroid profile after pregnancies complicated by maternal intrahepatic cholestasis differed greatly from that seen after uncomplicated pregnancy. Two main differences were found. In the disulfate fraction, the concentrations of two pregnanediol isomers, 5a-pregnane-3a,20a-diol and 5P-pregnane3a,20a-diol, were high after cholestasis. Other investigators have shown that, as a result of cholestasis, these pregnanediol sulfates circulate in greatly elevated amounts in the maternal plasma. Our results indicate that in cholestasis these steroids cross the placenta into the fetal compartment, where they circulate in elevated amounts as disulfates. Secondly, the concentrations of several steroid sulfates known to be synthesized by the fetus were significantly lower in the cholestasis group than in the healthy controls. This was especially true of 16a-hydroxydehydroepiandrosterone sulfate and 16a-hydroxypregnenolone sulfate. These results suggest that, in pregnancies complicated by maternal intrahepatic cholestasis, impairment of fetal steroid synthesis, and especially of 16a-hydroxylation, occurs in the fetal compartment.Thus, the changes in maternal steroid metabolism caused by cholestasis are reflected in the steroid profile of the fetoplacental circulation. Furthermore, maternal intrahepatic cholestasis may result in the production of some substance which crosses the placenta and affects fetal steroid metabolism.
Abstract-Three mass fragmentatographic methods for the determination of unconjugated estriol in pregnancy plasma and unconjugated and conjugated estriol in plasma of nonpregnant women after estriol administration were developed and tested as to their reliability and practicability. The methods were found to fulfii appropriate reliability criteria especially with regard to specificity. Unconjugated estriol could be assayed without prior chromatography in late pregnancy plasma, but a chromatographic step was needed for plasmas with a low estrioi titre, and both a methylation step and Chromatography is needed to achieve the required specificity if plasma conjugated estriol is determined or if assays are carried out following estrioi administration. Unconjugated estrioi in normal late pregnancy plasma was found in concentrations from 4.3 to 9.3 pg/L The highest value recorded, 16.3 pg/i, was found in a prediabetic subject with mild hypertension, who delivered a child weighing 4150 g by Cesarean section in the 39th week. Low values were found in severe hypertension and in toxemia, and in general the results from the pathological material investigated seemed to correlate well with the clinical findings. However, only a few samples (five to ten) can be processed so rapidly that the resuits can be obtained the same day, which in addition to the expensive and complicated instrumentation limits the usefulness of the methods in routine clinical chemistry.
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