- Email: [email protected]
291. Endocrine assessment of fetoplacental function
365
Abstracts Maternal plasma cholesterol is generally considered to be the main progesterone precursor in human pregnancy. However, during in vitro perfusion of the whole placenta as well as during incubation of slices or mitochondrial preparations, labelled cholesterol is poorly converted into progesterone. This low yield of transformation is probably due to the large amount of free or esterified endogenous cholesterol. Pregnenolone sulfate is very quickly metabolized during perfusion or incubation of slices; after 30 min, 70% of the total radioactivity is recovered as progesterone. In the same experimental conditions, cholesterol sulfate is hydrolyzed at a much lower rate than pregnenolone sulfate, for 50% remain unchanged after 2 h. Direct formation of pregnenolone sulfate has been demonstrated for the first time in this organ: The yield of conversion reaches 10 to 15% of total radioactivity recovered after 30min. In addition, the importance of cellular permeability for preferential utilization of radioactive precursors, as well as its better conservation during perfusion of the whole organ than during slice incubation, have been revealed by these different types of experiment. 291. Endocrine assessment of fetoplacental function
MACLW)D,S. C., SIMPSON,A. A. and LONGLEY,W. J., Departments of Obstetrics and Gynaecology, Physiology and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada The aim of the project is to determine the value of measurements of 24 h urinary estriol, serum total unconjugated estriol, estradiol, HCS and prolactin, individually or together, in identifying the existence of fetal malnutrition, fetal distress. or impending fetal death and in predicting fetal distress in utero or during delivery or asphyxia neonatorum. Serial daily measurements have been made on over 150 selected women following hospitalization for severe hypertension, diabetes, or fetal malnutrition prior to delivery. Approximately 45 infants either died, have been proven to be fetally malnourished, or developed fetal distress and/or asphyxia neonatorum. Normal urinary estriol level isagoodindicatoroffetoplacentalwell-being, however, when it is falling or low the fetus may not be at risk. Simultaneously low serum total unconjugated estriol measurements may improve the reliability of the diagnosis. Serum total unconjugated estradiol and HCS are of less value in identifying real or impending problems. Serum prolactin is abnormally elevated in several high risk pregnancies, particularly those complicated by severe hypertension. Serum estriol measurement alone may be no better than urinary estriol but may have an advantage in that the data would be available sooner since a 24 h collection is unnecessary. 292. Effect of dehydroepiandrosterone
(DHA) and dehydroepiandrosterone sulphate (DHAS) on the transformation of glucose to sorbitol by the human placenta SCIRPA,P.. MANGO, D., BOMPIANI. A. and MENINI.E.. Departments of Obstetrics and Gynaecology and Biological Chemistry, Catholic University, Rome, Italy
It is known that the placenta transforms glucose to sorbitol. a hexitol which is converted to fructose by the foetus. The purpose of this investigation was IO search for possible effects of foetal steroids on carbohydrate metabolism in the placenta. These effects, if present, could be interpreted as a
form of hormonal control of placental energy sources by the foetus. Incubations of 24,000 g supernatant fractions of human placentae in TRIS buffer, pH 7.4, containing glucose Cl4 0-j) (6 x 10-3M) and NADPH. have been nerformed with Bnd‘without the addition of dkhydroepiandrosterone (DHA) or its sulphate (DHAS). The following results have been obtained: (a) 6 x 10m4M concentrations of DHA consistently inhibited the reduction of glucose to sorbitol by 35-38x; (b) this inhibition diminished as lower concentrations of DHA were used; (c) under the same experimental conditions, 6 x lo-6M concentrations of DHA enhanced the production of sorbitol by 15-18:;; (d) 6x 10m6M concentrations of DHAS, increased sorbitol formation by 28-37”/,. The results obtained suggest that DHA and DHAS may be implicated in the control of sorbitol production by the human placenta. 293. Transplacental gradients in sex-hormone-binding globulin (SHBG) in human and simian pregnancy ANDERSON,D. C., FISHER,R. A., SHEPHERD,A. J., LASLEY,B. L. and HENDRICKX,A. G., St. Bartholomews Hospital, London; Primate Research Center, UC Davis; and Department of Reproductive Medicine, UCSD, LaJolla, California, U.S.A. It has been established that there is a large materno-fetal gradient in SHBG concentration at term, but the magnitude, cause and importance of this gradient is not known. The high maternal levels are an expected effect of estrogens, but low fetal levels are unexplained. Now, using a quantitative assay for SHBG, with SC+DHT as ligand, we have found the mean gradient in SHBG from mother to fetus to be 26-fold in 23 normal pregnancies, with no differences related to fetal sex, and similar gradients in twin pregnancies (n = 4). No correlation was found between maternal and fetal SHBG concentrations, suggesting they are independently determined; there was also no correlation with maternal HPL or urinary E3. Maternal and fetal levels in an anencephalic pregnancy were normal, suggesting that the fetal adrenal androgens are not causing low levels by inhibiting hepatic SHBG synthesis in the fetus. Preliminary data indicate that there is a similar materno-fetal SHBG gradient in the bonnet monkey (M. radiata). Since fetal 16a-hydroxylase activity is much lower in this species, this suggests that this enzyme is not involved directly or indirectly in inhibiting fetal SHBG synthesis. This monkey appears to be a useful model for further studies on the cause and effects of the transplacental SHBG gradient in pregnancy. 294. Effect of a diuretic on urinary excretion of estrogens in pregnant woman
ALEXANDER, S., STAVRIC, V.. SUGAR. J. and SCHWERS.J., Endocrine Research Unit, Department of Obstetrics and Gynaecology, Brussels University. Hospital St. Pierre. 1000 Brussels, Belgium The effect of 4-chloro-N-(2-furylmethyl)-sulfamyl-anthranilic acid (Lasix) on urinary excretion of total estrogens was investigated during the last trimester of pregnancy. Total estrogens were measured in serum and urine by radioimmunoassay. After a single i.m. administration of Lasix (40mg) in five subjects, urinary excretion increased during the first hour (34O”,bof control value) and returned to basal level around the tifth hour. Simultaneously serum estrogen concentration showed a smaller, but significant, elevation over the basal level (lO_20”~) and remained
Abstracts Maternal plasma cholesterol is generally considered to be the main progesterone precursor in human pregnancy. However, during in vitro perfusion of the whole placenta as well as during incubation of slices or mitochondrial preparations, labelled cholesterol is poorly converted into progesterone. This low yield of transformation is probably due to the large amount of free or esterified endogenous cholesterol. Pregnenolone sulfate is very quickly metabolized during perfusion or incubation of slices; after 30 min, 70% of the total radioactivity is recovered as progesterone. In the same experimental conditions, cholesterol sulfate is hydrolyzed at a much lower rate than pregnenolone sulfate, for 50% remain unchanged after 2 h. Direct formation of pregnenolone sulfate has been demonstrated for the first time in this organ: The yield of conversion reaches 10 to 15% of total radioactivity recovered after 30min. In addition, the importance of cellular permeability for preferential utilization of radioactive precursors, as well as its better conservation during perfusion of the whole organ than during slice incubation, have been revealed by these different types of experiment. 291. Endocrine assessment of fetoplacental function
MACLW)D,S. C., SIMPSON,A. A. and LONGLEY,W. J., Departments of Obstetrics and Gynaecology, Physiology and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada The aim of the project is to determine the value of measurements of 24 h urinary estriol, serum total unconjugated estriol, estradiol, HCS and prolactin, individually or together, in identifying the existence of fetal malnutrition, fetal distress. or impending fetal death and in predicting fetal distress in utero or during delivery or asphyxia neonatorum. Serial daily measurements have been made on over 150 selected women following hospitalization for severe hypertension, diabetes, or fetal malnutrition prior to delivery. Approximately 45 infants either died, have been proven to be fetally malnourished, or developed fetal distress and/or asphyxia neonatorum. Normal urinary estriol level isagoodindicatoroffetoplacentalwell-being, however, when it is falling or low the fetus may not be at risk. Simultaneously low serum total unconjugated estriol measurements may improve the reliability of the diagnosis. Serum total unconjugated estradiol and HCS are of less value in identifying real or impending problems. Serum prolactin is abnormally elevated in several high risk pregnancies, particularly those complicated by severe hypertension. Serum estriol measurement alone may be no better than urinary estriol but may have an advantage in that the data would be available sooner since a 24 h collection is unnecessary. 292. Effect of dehydroepiandrosterone
(DHA) and dehydroepiandrosterone sulphate (DHAS) on the transformation of glucose to sorbitol by the human placenta SCIRPA,P.. MANGO, D., BOMPIANI. A. and MENINI.E.. Departments of Obstetrics and Gynaecology and Biological Chemistry, Catholic University, Rome, Italy
It is known that the placenta transforms glucose to sorbitol. a hexitol which is converted to fructose by the foetus. The purpose of this investigation was IO search for possible effects of foetal steroids on carbohydrate metabolism in the placenta. These effects, if present, could be interpreted as a
form of hormonal control of placental energy sources by the foetus. Incubations of 24,000 g supernatant fractions of human placentae in TRIS buffer, pH 7.4, containing glucose Cl4 0-j) (6 x 10-3M) and NADPH. have been nerformed with Bnd‘without the addition of dkhydroepiandrosterone (DHA) or its sulphate (DHAS). The following results have been obtained: (a) 6 x 10m4M concentrations of DHA consistently inhibited the reduction of glucose to sorbitol by 35-38x; (b) this inhibition diminished as lower concentrations of DHA were used; (c) under the same experimental conditions, 6 x lo-6M concentrations of DHA enhanced the production of sorbitol by 15-18:;; (d) 6x 10m6M concentrations of DHAS, increased sorbitol formation by 28-37”/,. The results obtained suggest that DHA and DHAS may be implicated in the control of sorbitol production by the human placenta. 293. Transplacental gradients in sex-hormone-binding globulin (SHBG) in human and simian pregnancy ANDERSON,D. C., FISHER,R. A., SHEPHERD,A. J., LASLEY,B. L. and HENDRICKX,A. G., St. Bartholomews Hospital, London; Primate Research Center, UC Davis; and Department of Reproductive Medicine, UCSD, LaJolla, California, U.S.A. It has been established that there is a large materno-fetal gradient in SHBG concentration at term, but the magnitude, cause and importance of this gradient is not known. The high maternal levels are an expected effect of estrogens, but low fetal levels are unexplained. Now, using a quantitative assay for SHBG, with SC+DHT as ligand, we have found the mean gradient in SHBG from mother to fetus to be 26-fold in 23 normal pregnancies, with no differences related to fetal sex, and similar gradients in twin pregnancies (n = 4). No correlation was found between maternal and fetal SHBG concentrations, suggesting they are independently determined; there was also no correlation with maternal HPL or urinary E3. Maternal and fetal levels in an anencephalic pregnancy were normal, suggesting that the fetal adrenal androgens are not causing low levels by inhibiting hepatic SHBG synthesis in the fetus. Preliminary data indicate that there is a similar materno-fetal SHBG gradient in the bonnet monkey (M. radiata). Since fetal 16a-hydroxylase activity is much lower in this species, this suggests that this enzyme is not involved directly or indirectly in inhibiting fetal SHBG synthesis. This monkey appears to be a useful model for further studies on the cause and effects of the transplacental SHBG gradient in pregnancy. 294. Effect of a diuretic on urinary excretion of estrogens in pregnant woman
ALEXANDER, S., STAVRIC, V.. SUGAR. J. and SCHWERS.J., Endocrine Research Unit, Department of Obstetrics and Gynaecology, Brussels University. Hospital St. Pierre. 1000 Brussels, Belgium The effect of 4-chloro-N-(2-furylmethyl)-sulfamyl-anthranilic acid (Lasix) on urinary excretion of total estrogens was investigated during the last trimester of pregnancy. Total estrogens were measured in serum and urine by radioimmunoassay. After a single i.m. administration of Lasix (40mg) in five subjects, urinary excretion increased during the first hour (34O”,bof control value) and returned to basal level around the tifth hour. Simultaneously serum estrogen concentration showed a smaller, but significant, elevation over the basal level (lO_20”~) and remained