Whereas maternal venous levels of progesterone and oestrogens have been studied intensively in relation to parturition, little attention has been directed to fetal levels. In this study progesterone, oestrone (E1), oestriol (E2) and oestriol (E3) were measured in umbilical artery (UA) and umbilical vein (UV) serum at vaginal delivery (after induced or spontaneous onset of labour) and at elective Caesarean section. At least 14 samples were included in each group. All UV serum steroid levels were consistently higher than UA serum steroid levels. Cord serum levels of progesterone and arterio-venous differences were higher at vaginal delivery than at Caesarean section although maternal levels changed little. E1 and E2 levels were similar after spontaneous labour and at Caesarean section but were higher (P less than 0-05) after induced labour although E3 levels did not alter. E1 and E2 were higher and progesterone lower in primiparae than in multiparae. Fetal sex made no differences. These results suggest that induction of labour with oxytocin results in altered fetal hormone levels, that maternal hormone levels provide a poor reflection of fetal changes,and that current views about the mechanism of the onset of labour in animals may not be appropriate for man.

The urinary excretion patterns of oestrogen metabolites, including unusual metabolites, were determined by gas chromatography and mass spectrometry for 63 women with advanced breast cancer and 39 normal postmenopausal women. The concentration of total unusual metabolites excreted was found to be an excellent discriminant between breast-cancer patients and controls (P less than 0.0001). Discrimination between responders and non-responders to endocrine therapy was attempted, using several different indices. Of these, the ratio of Classical Oestrogens to Unusual Metabolites (CE/UM) proved a fair discriminant, but the product of this ratio and the oestriol ratio (CE/UM x E3R) was much the best discriminant. This product, termed a Pattern Index, has considerable potential, not only as a discriminant for selecting therapy, but also as a rapid index of patient response to that therapy.

Various doses (1 microgram to 10 mg) of oestriol (E3) were intraperitoneally injected into mice immediately after subcutaneous inoculation of an oestrogen receptor-negative lymphoma cell line (KE-5) established from a spontaneously developed AKR thymic lymphoma. The growth of KE-5 cells was markedly promoted by E3 at the early stage of tumour growth. At this stage, 1 microgram E3 enhanced tumour growth significantly and the maximum effect was obtained with 1 mg E3. Normal female mice showed a higher incidence and shorter latency than males. However, once tumours became palpable, the tumour growth rate appeared to be unaffected. Histological observations using Alcian blue and colloidal iron revealed a marked increase of hyaluronic acid in the subcutaneous connective tissue of the tumour-injection site within 3-5 days after intraperitoneal administration of 1 mg E3. Biochemical analyses showed a rapid and marked increase in skin hyaluronic acid content to over 3 times the control levels (0.25 +/- 0.10 mg g-1 skin) within 3 days of E3 administration. Subcutaneous inoculation of KE-5 cells together with hyaluronic acid (0.2 mg) resulted in markedly enhanced tumour growth, particularly at the early stage. These results suggest that an increase in stromal hyaluronic acid content is the most likely mechanism responsible for the promoting effect of E3 on KE-5 cells.

Forty nulliparous patients with Bishop score of 3 or less were given 15 mg oestriol gel, 10 mg PGF2 alpha gel or gel alone via the extra-amniotic route. Both the oestriol and prostaglandin treated patients had a significant increase in Bishop score and a significant reduction in induction-delivery interval compared to controls. Oestriol gel had significantly less stimulatory effect on uterine activity than prostaglandin gel, indicating a possible local action.

In a randomised double-blind study 568 women were given orally either 15 mmol magnesium-aspartate hydrochloride per day or aspartic acid as placebo. The outcome of pregnancy was significantly improved in the magnesium group (fewer maternal hospitalisations, reduction in preterm delivery and less frequent referral of newborn to the neonatal intensive care unit). In the 437 patients with regular intake of tablets, haematocrit, haemoglobin and calcium show a decrease up to 20 weeks of gestation (wks) and an increase during the last 8 wks, whereas magnesium stays at a low level. Oestriol and HPL are rising steadily during gestation. In all parameters, no differences were found between the magnesium and placebo group, except for a higher level of oestriol at 33 to 36 wks and a lower level above 36 wks in the magnesium group. Because of the numerous benefits throughout the pregnancy magnesium supplementation is recommended for all pregnancies.

Plasma unconjugated oestriol (E3) concentrations were determined by radioimmunoassay in 10 normal subjects in late pregnancy, throughout a normal day and night, and after a 50 g oral glucose load. There was a circadian pattern in E3 concentration characterized by an abrupt increase of 15 per cent at night. There was no significant rhythm during the day or night, taken separately. However there was a 10 to 11 per cent reduction in E3 concentrations soon after some meals and after a glucose load, possibly due to expansion of the plasma volume. Excluding the effect of meals, the fluctuation of E3 concentrations in individuals (median of the coefficients of variation) was 11.5 per cent in the day. Overall, it was 13.2 per cent in the day, 12.1 per cent at night and 15.9 per cent over the whole period studied. Since the variation in plasma unconjugated E3 concentrations through 24 hours was no greater than random fluctuations or day-to-day variation there is no need to restrict the time of blood sampling in clinical practice.

A simple and rapid method is described for the quantitative determinations of free and conjugated oestrogens in pregnancy urine. The oestrogens are precipitated with ammonium sulphate and freed from non-oestrogenic compounds by solvent extraction. The conjugated oestrogens are hydrolysed by a beta-glucuronidase from Escherichia coli, and the total free oestrogens are extracted into ether and their fluorescence intensity at 310 nm in this solvent is determined. The method is rapid and precise for oestrogen levels at concentrations greater than 2 mug/ml (7 mumol/1). It is proposed that this method, which measures oestradiol and oestriol levels, be applied routinely to monitor feto-placental function in pregnancy. It offers advantages over other currently used assays in that less manipulative and technical skill is required to give a high level of precision and accuracy. An accurate estimate can be produced within 30-60 min of receipt of a 24-h uring specimen. Two variations of the method are also described. In one the ammonium sulphate precipitation step is omitted so as to give an even quicker assay procedure which determines conjugated oestrogens in the urine, and in the other oestriol only is determined.

Oestriol profile represents a functional parameter of the foetal placental unit. Basing on the fact that maternal cortisol regulates oestriol production via a negative feedback action on foetal hypothalamus, relative low serum oestriol concentrations in the morning are compared with increasing oestriol concentrations in the evening, spaced out at short-time intervals, pointing to a dynamic oestriol production of the foetal placental unit. The mean oestriol concentration in the morning and maximum peak values in the evening were determined as criteria of the oestriol profile. In normal pregnancies (n = 74) the oestriol concentration in the morning increases from an average value of 8.0 ng/ml in the 32nd/33rd week to 11.6 ng/ml in the 40th/41st week of gestation. During the same period the peak values in the evening rise from 8.8 to 15.9 ng/ml. The mean cortisol concentrations in normal pregnancies (n = 49) from 32nd to 41st week are in the range of 333 +/- 88 ng/ml in the morning and 205 +/- 66 ng/ml in the evening. There is no significant difference between individual weeks. The predictive value of the oestriol profile was assessed regarding the foetal outcome of 55 high-risk pregnancies. 32 newborn infants exhibited intrauterine growth retardation with birth weights below the 10th and 5th percentile, respectively. In this group 6 patients exhibited low oestriol values in the morning, whereas 12 demonstrated a pathological profile in the evening. In 11 of 12 high-risk pregnancies exhibiting pathological oestriol profile growth, retardation of the newborn was found to be below the 5th percentile. Cortisol concentrations do not significantly differ between normal and high-risk pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Six patients each with a very low 24-hour urine oestriol excretion were infused with hypertonic dextrose and amino acids for 48 hours prior to delivery. Amniotic fluid samples were studied before and after infusion. Lecithin sphingomyelin ratios and insulin levels were increased following infusions in all patients. There was usually a fall in amniotic fluid glucose and an increase in ammonia, amino acid nitrogen and osmolality following infusions. Maternal plasma oestriol, human placental lactogen, cystyl aminopeptidase and urine oestriol excretion were unchanged during the infusions.

We describe the specificity profile and V region sequences of a high-affinity monoclonal antibody (mAb), 3910, directed against oestrone-3-glucuronide (E3G). Inhibition studies show that the D-ring is critical for steroid specificity, while the glucuronic acid attached to the A ring is required for high binding affinity, suggesting that both 'ends' of the E3G ligand are recognized. The VH domain is encoded by a gene from the VH7183 family, while VL appears to be encoded by the Vk5.1 gene (kappa II subgroup) with a deletion of six residues from complementarity-determining region-1 (CDR1). The VH CDR3 is 10 amino acid residues in length, of which D/N contributes five residues. Comparison of VH CDR of 3910 with those of mAb against progesterone (DB3) and digoxin (26-10, 40-50), for which crystal structures have been determined, suggests that aromatic side chains are important for E3G binding and that tyrosine residues H50, H97 and H100 may interact with the ligand. The Fab fragment of 3910 has been crystallized in its native and steroid (E3G and oestriol-3-glucuronide) complexed forms. An X-ray diffraction data set to 3 A resolution has been collected for the native Fab.

Serum zinc concentrations in 234 gravidae showed a gradual fall during the first and second trimesters. From the 25th week of gestation until delivery there is a levelling out of mean zinc values. No correlations between serum zinc, serum HCS, or urinary excretion of oestriol were found. Women with mature infants born by normal delivery showed significantly higher serum zinc during pregnancy than women with abnormal deliveries and/or abnormally developed infants (p less than 0.001). Eight infants showed congenital malformations. Five of the 8 mothers showed the lowest serum zinc concentrations recorded during respective week of pregnancy. A diabetic woman gave birth to an immature infant with multiple skeletal malformations. She showed the lowest serum zinc in the 21st week, and at the same time a very low alkaline phosphatase activity. Her serum proteins and serum HCS were normal. Women with dysmature infants showed significantly lower zinc values during pregnancy (p less than 0.02) than women with mature infants born by normal delivery. Data from studies on zinc metabolism show that there is a requirement of at least 375 mg of zinc during pregnancy in order to meet the demands of normal weight gain. Teenagers, women with multiple pregnancies, women with impaired intestinal absorption due to disease or drugs and in particular women with a low-protein, high-phytate diet seem to risk developing zinc deficiency during pregnancy.

The effects on blood-clotting factors, plasma lipids and endometrial proliferation of two types of oral oestrogen therapy (a) cyclical therapy with 0.625 mg/day conjugated equine oestrogens for 3 wk followed by 1 wk without treatment, and (b) continuous therapy with 2 mg/day oestriol) were investigated in a 5-mth study involving 22 post-menopausal women. Assays were performed in order to measure blood-clotting factors (activity of the factor II-VII-X complex, anti-thrombin III, euglobulin lysis time) and plasma lipids (total cholesterol, triglycerides, lipoprotein electrophoresis) before treatment and after 3 and 4 mth of treatment. The only significant change found to have occurred was a decrease in the beta: alpha lipoproteins ratio; this was greater in the group treated with conjugated equine oestrogens, but was also statistically significant in the group treated with oestriol. Endometrial proliferation was investigated indirectly by means of the medroxyprogesterone acetate (MPA) test before treatment and after 5 mth of treatment. The response to MPA at the end of 5 mth of treatment in patients previously unresponsive, showed endometrial proliferation to have occurred during treatment with conjugated equine oestrogens but not during treatment with oestriol.

The effect of the oestrogens, oestradiol and oestriol, on plasma albumin dynamics in the uterus was studied in mice. A double isotope technique with 125I- and 131I-labelled human serum albumin was used. The optimum conditions to measure the extravascular accumulation of albumin were to use one labelled albumin as "permeability marker" (30 min circulation time) the other as plasma volume indicator (3 min circulation time). The oestrogens increased the extravascular accumulation of labelled albumin in the uterus but not in diaphragm or heart muscle. The accumulation was maximal after 4 h (75% higher than in controls) and was significant as early as 2 h after oestrogen administration. It cannot be decided whether the increase in labelled albumin accumulation was due to an increase in permeability and/or to an increase in the total surface area of perfused capillaries.

Corticosteroid binding globulin (CBG) concentrations in maternal plasma have been measured throughout pregnancy in a series of 100 singleton pregnancies in 89 normotensive women. Plasma CBG concentrations were monitored also in 10 women with essential or renovascular hypertension. Plasma albumin, cortisol and oestriol were measured concurrently. Plasma CBG increased two and a half to three times during pregnancy. In those women who developed hypertension in pregnancy (mean arterial pressure greater than 107 mmHg), the plasma CBG concentrations were significantly lower than in those who remained normotensive. In women who developed hypertension, the CBG either failed to increase at the same rate as in normal pregnancies or the level fell before the appearance of hypertension. The earlier the onset of hypertension, the greater the decline in CBG. In all subjects, the CBG concentration at 34-36 weeks gestation was directly related to the birthweight of the infant. Plasma cortisol levels were depressed in hypertension relative to that in the normotensive women. Whilst plasma albumin levels decreased at least 30% in most women during pregnancy, the fall tended to be less in hypertensive women, but there was marked overlap between patient groups. Plasma oestriol concentrations were depressed only in the very severely affected cases. It is suggested the CBG concentration is a further reflection of the metabolic abnormalities associated with hypertension in pregnancy, and that it can be used as a marker to identify and monitor those patients at risk.

The preparation of pure oestradiol-17beta-3-hemisuccinyl-bovine serum albumin conjugate is described. Contrary to previous findings this antigen raised reasonably specific antisera in rabbits which possessed a cross reaction of only 2.0% with oestrone, and 0.8% with oestriol. The production of this specific antisera is considered to be due to the high purity of the antigen. The role of the C-3 phenolic hemisuccinyl linkage of the antigen in raising this specific antisera is discussed.

Simple diffusion experiments indicated that oestriol was retained by human pregnancy plasma more effectively than by albumin solutions of a corresponding concentration. Oestriol bound (Ka = 6 X 10(6) l/mol at 4 degrees C) to a glycoprotein which had been isolated from plasma by adsorption to Concanavalin A. The free energy of binding at 37 degrees C was -38 kJ/mol. Competition experiments indicated that the oestriol binding glycoprotein had properties expected of sex hormone binding globulin. The distribution of oestriol among the protein fractions of human pregnancy plasma--glycoprotein bound 7.8%, albumin bound 78.6%, unbound 13.6%--suggests that this glycoprotein plays little part in the transport of oestriol.

Intrauterine pressure was recorded in anaesthetized rats on Day 20 of pregnancy by the replacement of a conceptus with a balloon. Intrauterine pressure in ovariectomized pregnant rats treated with progesterone alone was markedly higher than that in intact pregnant rats, but treatment with oestradiol as well reduced values to those of controls. Oestriol and oestrone were less effective. Uterine tolerance, tested by increasing the balloon volume until the uterus ruptured, was greater than 6.5 ml in intact rats and in ovariectomized rats treated with progesterone + oestradiol, but rupture occurred at a volume of 4.3 ml when progesterone alone was used. One of the roles of oestrogen during late pregnancy in rats may be to ensure sufficient plasticity of the uterus to allow for the increase in conceptus size.

The aim of the study was estimation of endocrinological function of placenta in pregnancy complicated by GDM. The study were performed on a group 13 women with GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and intensive insulinotherapy with self monitoring levels of glucose. In women with GDM level of fructosamine and HbAlc were significant higher but in normal range. In 28, 36, 37, 38, 39 week of pregnancy were determined levels of hPL, oestriol and progesterone in serum and daily excretion of oestrogens in urine. From 36 week of pregnancy levels of hPL, oestriol and progesterone were significant lower in women with GDM. In 39 week of pregnancy level of hPL was 9.34 micrograms/ml vs. 12.71 micrograms/ml, p < 0.01, oestriol was 495.77 nmol/l vs. 681.14 nmol/l, p < 0.01 and progesterone was 25.12 ng/ml vs. 34.52 ng/ml, p < 0.01 respectively in women with GDM and in normal pregnancy.

The serum concentrations of HCG, HPL, progesterone and oestriol and ultrasonic findings were compared with one another in 42 women with normal pregnancy course, 51 women with haemorrhages and abortion and 27 women with haemorrhages and delivery on time. Correct diagnosis was most frequently possible with the help of ultrasound examination. However, it was possible to improve the accuracy of the diagnosis before the twelfth week of pregnancy by means of hormone analysis. If the hormone concentrations were normal, whereas ultrasound findings were either negative or not clear, intact pregnancy could be assumed. HCG and progesterone determination possessed the advantage of being reliably measurable even before cessation of menstrual bleeding. From the eighth to ninth weeks of pregnancy, determinations of HPL were also suitable for assessing endocrinal functions. After the twelfth week of pregnancy, the pregnancy conditions could be judged most safely by the ultrasound method.

In present day, recognized factors which influence the carbohydrate metabolism of a diabetic during pregnancy have been reviewed. Possible effects on the fetus are discussed. Based on the good results obtained by Roversi and Canussio with the "Maximal tolerated dose of insulin", a state of glycemia within the normal limits was sought; this aim is attained most readily with a 3-4 times daily injection of soluble insulin. With satisfactory control of metabolism and regular surveillance of fetal parameters (ultrasonics, CTG, oestriol, HPL), the time for delivery can approach the calculated date: thus, the danger of fetal respiratory distress is reduced. Also, fetal hyperinsulinism can be avoided by stabilising the diabetic condition as early as possible within the normal limits of glycemia. Spontaneous birth is attempted with preparations made for caesarean section.

The effect of oestriol (3 mg for 3 mth), oestradiol valerate (2 mg for 3 mth) and ethinyloestradiol (0.025 mg for 21 days) on sex hormone binding globulin (SHBG), transcortin, ceruloplasmin and pregnancy-associated macro-globulin (PAG) was analysed in oestrogen-deficient women. The doses of oestrogens were therapeutically effective for the treatment of oestrogen-deficiency symptoms. Treatment with 0.025 mg ethinyloestradiol induced a 281% increase in PAG, a 119% increase in SHBG, a 74% increase in transcortin and a 74% increase in ceruloplasmin levels. Administration of 2 mg oestradiol valerate resulted in a 40% increase in SHBG, a small increase in transcortin and ceruloplasmin, whereas PAG levels remained unaffected. None of the parameters tested were affected by oestriol treatment. PAG was clearly the most sensitive parameter for ethinyloestradiol while SHBG was the most sensitive parameter for oestradiol valerate. These results show no relationship between clinical efficacy and effect of plasma protein synthesis, and demonstrate that one has to be very careful when comparing potency estimates for different oestrogens and different parameters.