British Journal of Obstetrics and Gynaecology February 1979. Vol86. pp 119-124
THE COMPARTMENTAL DISTRIBUTION OF OESTROGENS AND PREGNANCY SPECIFIC p1 GLYCOPROTEIN BY
R . SMITH, MRC Research Fellow
A. KLOPPER, Professor of Reproductive Endocrinology G. HUGHES,Senior Registrar AND
G. WILSON,Biochemist Department of Obstetrics and Gynaecology, University of Aberdeen University Medical Buildings, Foresterhill, Aberdeen, AB9 2 2 0
Summary Pregnancy specific p1 glycoprotein (PSp,G), unconjugated oestriol, total oestriol and oestradiol were measured in the peripheral venous blood of 25 pregnant women. The results were compared with similar measurements in maternal tissue fluid, cerebrospinal fluid, and uterine vein blood ; or with retroplacental blood, umbilical cord blood, and amniotic fluid. The highest mean concentration of PS&G occurred in maternal venous blood and was 17.37 (SD 7.07) mg/dl. The mean peritoneal value was 21 per cent of the mean peripheral vein value. Two tissue fluid values were 32 per cent and 5 per cent of the corresponding peripheral vein values. No measurable amount of PS&G was found in maternal cerebrospinal fluid and cord artery. Unconjugated oestriol was found in highest concentration in retroplacental blood. The concentration fell from here to contiguous compartments. An exchange between these compartments was suggested by significant correlations in their oestriol content. Conjugated forms of oestriol, as represented by the measurement of total oestriol, were present in highest concentration on the fetal side in cord arterial blood, but could be found in all other compartments. Oestradiol appeared in highest concentrations in retroplacental blood. Low values of oestradiol were found in the fetal compartment. Correlations between maternal compartments were few and this was considered evidence of impeded transmission between these compartments. THISstudy was designed to examine the spread of oestrogens through the fetal and maternal compartments from their point of production in the fetoplacental unit, and to compare this with the distribution of pregnancy specific PI glycoprotein (PSp,G). Although the final step in the biosynthesis of oestriol and oestradiol
probably takes place in the placenta, it seemed relevant to examine separately the distribution of the fetoplacental oestrogen, oestriol, and of the purely placental oestrogen, oestradiol. The molecular sizes of oestriol and its various conjugates such as oestriol-3-sulphate and oestriol-16 glucosiduronate are not greatly 119
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different, but their lipophilic characteristics and hence their likely transmission rates across the membrane barriers between compartments differ greatly. We have therefore measured separately unconjugated oestriol and total oestriol, a mixed entity consisting almost entirely of the conjugated forms. For contrast we have examined the distribution of a much larger molecule, the protein PSP,G which, like the steroids, is also believed to originate from the trophoblast (Tatarinov et al, 1976), expecting that, because of its size, the pattern of its distribution should be quite different. It was hoped that this comparison of the compartmental distribution of various placental products would give some insight into the site and nature of their physiological action in pregnancy. SUBJECTS AND METHODS Twenty-five patients consented to the collection of samples. These were mainly women having an elective Caesarean section within a week of term. Permission for the study was obtained from our local ethical committee. Two samples of tissue fluid were collected in different ways. In one case on the day before delivery a small intravenous cannula was placed in the pretibial pad of oedema. The small
sample obtained was just sufficient to measure PSP,G and relate this to a simultaneous venous blood value. A second sample of tissue fluid from another patient was obtained from an excised abdominal scar with its underlying fat, which exuded sufficient fluid in the time taken to complete the operation for all the parameters to be measured. Cerebrospinal fluid was collected at the time of spinal anaesthesia. Peripheral venous blood was taken before delivery of the baby. Only clear samples of peritoneal fluid and amniotic fluid were analysed. Uterine vein blood was withdrawn from one of the wide bore veins running lateral to the uterus in the broad ligament; any bleeding which followed ceased as soon as the baby was delivered. Cord artery and vein blood was collected after clamping and dividing the cord and before delivery of the placenta. Retroplacental blood, taken to be the dark blood which appears from behind the separating placenta, was allowed to run into a small bowl at the uterine incision. The heparinized blood samples were separated after centrifugation and the plasma stored a t -20°C. Samples from the same patient were measured on the same assay run. Unconjugated oestradiol was measured by a specific radioimmunoassay, using antisera
TABLE I Oestrogens and PSPIC in maternal and fetal compartments Placental product
Cere- Peritoneal Peripheral Intervein stitial brospinal fluid fluid fluid
PSp,G Range 1.34,4.8 (rng/dl) Mean 3.07 SD No. 2
Uterine vein
Retroplacental blood
Cord vein
~ 0 . 21.14-6.37 5.62-32.80 5.83-33.62 2.84-25.62 1 0 . 2 4 . 4 4 3.71 17.37 16.55 12-63 0.07 1.88 7.07 7.39 6.54 2 12 23 17 20 16
Cord artery
THE COMPARTMENTAL DISTRIBUTION OF OESTROGENS AND PREGNANCY SPECIFIC p1 GLYCOPROTEIN BY
R . SMITH, MRC Research Fellow
A. KLOPPER, Professor of Reproductive Endocrinology G. HUGHES,Senior Registrar AND
G. WILSON,Biochemist Department of Obstetrics and Gynaecology, University of Aberdeen University Medical Buildings, Foresterhill, Aberdeen, AB9 2 2 0
Summary Pregnancy specific p1 glycoprotein (PSp,G), unconjugated oestriol, total oestriol and oestradiol were measured in the peripheral venous blood of 25 pregnant women. The results were compared with similar measurements in maternal tissue fluid, cerebrospinal fluid, and uterine vein blood ; or with retroplacental blood, umbilical cord blood, and amniotic fluid. The highest mean concentration of PS&G occurred in maternal venous blood and was 17.37 (SD 7.07) mg/dl. The mean peritoneal value was 21 per cent of the mean peripheral vein value. Two tissue fluid values were 32 per cent and 5 per cent of the corresponding peripheral vein values. No measurable amount of PS&G was found in maternal cerebrospinal fluid and cord artery. Unconjugated oestriol was found in highest concentration in retroplacental blood. The concentration fell from here to contiguous compartments. An exchange between these compartments was suggested by significant correlations in their oestriol content. Conjugated forms of oestriol, as represented by the measurement of total oestriol, were present in highest concentration on the fetal side in cord arterial blood, but could be found in all other compartments. Oestradiol appeared in highest concentrations in retroplacental blood. Low values of oestradiol were found in the fetal compartment. Correlations between maternal compartments were few and this was considered evidence of impeded transmission between these compartments. THISstudy was designed to examine the spread of oestrogens through the fetal and maternal compartments from their point of production in the fetoplacental unit, and to compare this with the distribution of pregnancy specific PI glycoprotein (PSp,G). Although the final step in the biosynthesis of oestriol and oestradiol
probably takes place in the placenta, it seemed relevant to examine separately the distribution of the fetoplacental oestrogen, oestriol, and of the purely placental oestrogen, oestradiol. The molecular sizes of oestriol and its various conjugates such as oestriol-3-sulphate and oestriol-16 glucosiduronate are not greatly 119
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different, but their lipophilic characteristics and hence their likely transmission rates across the membrane barriers between compartments differ greatly. We have therefore measured separately unconjugated oestriol and total oestriol, a mixed entity consisting almost entirely of the conjugated forms. For contrast we have examined the distribution of a much larger molecule, the protein PSP,G which, like the steroids, is also believed to originate from the trophoblast (Tatarinov et al, 1976), expecting that, because of its size, the pattern of its distribution should be quite different. It was hoped that this comparison of the compartmental distribution of various placental products would give some insight into the site and nature of their physiological action in pregnancy. SUBJECTS AND METHODS Twenty-five patients consented to the collection of samples. These were mainly women having an elective Caesarean section within a week of term. Permission for the study was obtained from our local ethical committee. Two samples of tissue fluid were collected in different ways. In one case on the day before delivery a small intravenous cannula was placed in the pretibial pad of oedema. The small
sample obtained was just sufficient to measure PSP,G and relate this to a simultaneous venous blood value. A second sample of tissue fluid from another patient was obtained from an excised abdominal scar with its underlying fat, which exuded sufficient fluid in the time taken to complete the operation for all the parameters to be measured. Cerebrospinal fluid was collected at the time of spinal anaesthesia. Peripheral venous blood was taken before delivery of the baby. Only clear samples of peritoneal fluid and amniotic fluid were analysed. Uterine vein blood was withdrawn from one of the wide bore veins running lateral to the uterus in the broad ligament; any bleeding which followed ceased as soon as the baby was delivered. Cord artery and vein blood was collected after clamping and dividing the cord and before delivery of the placenta. Retroplacental blood, taken to be the dark blood which appears from behind the separating placenta, was allowed to run into a small bowl at the uterine incision. The heparinized blood samples were separated after centrifugation and the plasma stored a t -20°C. Samples from the same patient were measured on the same assay run. Unconjugated oestradiol was measured by a specific radioimmunoassay, using antisera
TABLE I Oestrogens and PSPIC in maternal and fetal compartments Placental product
Cere- Peritoneal Peripheral Intervein stitial brospinal fluid fluid fluid
PSp,G Range 1.34,4.8 (rng/dl) Mean 3.07 SD No. 2
Uterine vein
Retroplacental blood
Cord vein
~ 0 . 21.14-6.37 5.62-32.80 5.83-33.62 2.84-25.62 1 0 . 2 4 . 4 4 3.71 17.37 16.55 12-63 0.07 1.88 7.07 7.39 6.54 2 12 23 17 20 16
Cord artery
