Factor VIII related antigen (VIIIRAg), Factor VIII coagulant activity (VIIIC), plasma uric acid, total plasma oestriol, plasma human placental lactogen (hPL) and urine oestrogen/creatinine ratio were measured in a group of 21 patients clinically suspected of fetal growth retardation and compared with normal pregnancy. Of the hormone assays, hPL was better than either oestrial or oestrogen/creatinine ratio at distinguishing between normal and growth retarded pregnancies. Uric acid levels tended to be higher than normal in patients with fetal growth retardation, but the best means of distinguishing normal from growth retarded pregnancies proved to be the VIIIRAg/VIIIC ratio. This ratio was significantly elevated in fetal growth retardation compared with normal pregnancy, and the increase was evident as early as 30 weeks gestation. Using the VIIIRAg/VIIIC ratio test, the outcome of 17 of the 21 suspect pregnancies could be correctly predicted.

The performance of clinical chemistry laboratories in New Zealand in the assays of oestriol and creatinine in pregnancy urine has been investigated. The quality of oestriol determinations in general was poor. Only seven of 20 laboratories achieved an inter-assay precision of better than 12 percent consistently through the range of oestriol levels represented by three control urines. The precision of laboratories in assaying urinary creatinine was, however, of a higher standard. Only three of 18 laboratories had precision values that could be regarded overall as unsatisfactory.

Plasma levels of unconjugated and total oestriol and urinary excretion of oestriol were measured in ten healthy women with uncomplicated pregnancy and with normal renal function. A significant correlation between plasma total oestriol and urinary oestriol was found in five out of ten patients and between plasma total and unconjugated oestriol in only four of ten patients. When the data from the ten patients were combined there were significant correlations between urinary oestriol and the two plasma oestriol species as well as between plasma unconjugated and total oestriol. The mean urinary oestriol excretion correlated significantly with the mean urine volume. No significant correlation was found in the individual subjects between oestriol clearance and creatinine clearance, but the combined data from the ten patients yielded a highly significant correlation. The differences within or between days was highest for plasma unconjugated oestriol and lowest for urinary oestriol/mmol of creatinine. Over a three to four day period, a drop of 20 per cent in urinary oestriol/mmol of creatinine, 25 per cent in urinary oestriol/24 hours, 35 percent in plasma total oestriol and 40 per cent in plasma unconjugated oestriol do not necessarily indicate fetal danger.

43 patients with colpitis maculosa (average age 60.2 years) were selected for an open control therapeutic study with Ortho-Gynest vaginal cream (Ortho-Cilag). The cream contains 0.5 mg of oestriol per single applicator filling. The treatment lasted from 3 to 4 weeks, success being evaluated by clinical documentation and cytological evaluation of vaginal smears before and after treatment. 10 patients (23.3%) were treated successfully, 29 (67.4%) showed a distinct improvement both clinically and cytologically, whilst the remaining 4 (9.3%) showed only moderate improvement. Hence, 39 patients (90.7%) were classified as having been successfully or partly successfully treated. Severe symptoms disappeared completely or were greatly alleviated in 91.4% cases. Moderate symptoms vanished in 59.7%. 58.1% showed a complete normalisation of the former atrophic vaginal skin. Blood spotting and reddening of the vaginal wall vanished completely. A change from dry to moist vagina occurred in 77.3% patients. Discharge vanished completely in 80.6% cases. No untoward side effects were recorded.

The clinical usefulness was assessed of ultrasonography in the study of fetal hypotrophism determining the parameters BIP, THQ and placental parameters. Fetal growth was assessed and in case of hypotrophism adequate therapeutic management was undertaken. The study was carried out on 56 pregnant women referred for diagnosis and treatment of fetal hypotrophism in the period 1983-1985. The control group comprised 56 women with physiological pregnancy. The study was carried out with examinations at weekly intervals from the 24th week of pregnancy till labour using a Hellige-Panavista unit with a 2.5 MHz probe. The BIP and THQ dimensions were calculated a together with placental parameters. The oestriol level was determined in 24-hour urine. The underlying disease and fetal hypotrophism were treated. The most valuable indicator for the determination of asymmetrical and symmetrical type of hypotrophism and for its monitoring was the BIP/THQ index. Ultrasonography makes possible a rapid and accurate diagnosis of fetal condition and control of its treatment. Ultrasonographic observation of the placenta is a source of valuable information for the obstetrician. Oestriol determination is without any greater significance for monitoring of fetal hypotrophism.

This study developed and validated a sensitive analytical method for simultaneous screening of four classes of endocrine-disrupting chemicals (i.e. progestogens, androgens, oestrogens and phenols) in milk and powdered milk using ultra-performance liquid chromatography (UPLC) coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry (QTOF-MS). Dansylation of oestrogens and phenols enhanced the ionisation efficiency and shifted the ionisation mode from negative to positive, which allowed for the simultaneous analysis of four EDCs in one chromatographic run. An efficient sample pre-treatment minimised the matrix effects. The mass errors for the precursor and product ions for 26 target compounds varied between -2.8 and 2.3 mDa; and the limits of detection (signal-to-noise ratio = 3) for milk and powdered milk were less than 0.04 µg l(-1) and 0.10 µg kg(-1), respectively. The proposed method was successfully used to analyse multiple types of real samples, including normal temperature whole milk, infant formula and whole powdered milk. In 11 samples, two target compounds, progesterone and androstenedione, were detected. The progesterone concentrations ranged from 8.1 to 12.7 µg l(-1) in milk, and from 1.2 to 32.0 µg kg(-1) in infant formulas and whole powdered milks. The androstenedione concentrations varied from 0.39 to 0.79 µg l(-1) in milks, and from 0.29 to 1.2 µg kg(-1) in infant formulas and whole powdered milks. Two post-target compounds, one isomer of oestriol and 5α-dihydroprogesterone, were tentatively identified by post-target analysis in two of 11 real samples.

The concentration of oestriol and the proportion of this hormone not bound to plasma protein were measured using radioimmunoassay and centrifugal ultrafiltration respectively, in 55 samples of plasma obtained from 12 women in the last 2 to 7 weeks of uncomplicated pregnancy. Among individuals, the mean plasma concentration of oestriol varied from 25.8 +/- 94.8 nmol/l; in nine subjects, there was a tendency for oestriol concentrations to increase as delivery approached. The mean proportion of oestriol not bound to plasma protein in the different subjects varied from 13.1 to 18.9%, but values from any individual subject remained essentially constant during the periods of study. These measured values were used to calculate, for each sample, the apparent concentration of oestriol not bound to plasma protein. The results were combined with analogous values for oestradiol and progesterone obtained from the same plasma samples and described in a previous study. It was found that the mean ratio of the concentration of oestriol and oestradiol was 0.75, the mean concentration of non-protein-bound oestriol was 8.7 times that of non-protein-bound oestradiol, and in individual subjects, there was no consistent trend as delivery approached in the ratio of the concentration of progesterone to that of oestriol in either the total or non-protein-bound form.

Maternal and foetal plasma collected at normal delivery and at elective caesarean section was assayed for sex steroid levels. Foetal cord plasma concentrations of progesterone, 17-hydroxyprogesterone, oestrone and oestriol were higher than maternal values at normal delivery, whereas oestradiol levels were lower. Oestrone concentrations were higher than oestradiol in the foetal circulation at normal delivery and oestrone values were higher following normal delivery than at elective caesarean section.

Samples and data were collected from twenty-eight female black rhinoceroses (Diceros bicornis) during translocation efforts carried out by the Department of National Parks and Wildlife Management in Zimbabwe. Biological data were collected, cytological examination of vaginal smears was performed, and serum concentrations of follicle stimulating hormone, luteinizing hormone, progesterone, oestriol, and 17-beta-oestradiol were determined by radio-immuno-assay. Prolactin levels were determined for 3 pregnant animals, 1 of which was sampled before and after parturition. Vaginal cytology was not found to be helpful for indicating the oestrous cycle stage for the black rhinoceros, but progesterone and 17-beta-oestradiol levels were found to be useful indicators of pregnancy and possibly of oestrous cycle stage as well.

Prostaglandins E and F2 alpha as well as two steroid hormones, progesterone and unconjugated oestriol, were measured in amniotic fluid of 30 diabetics. The prostaglandin levels of all patients went up with significance after the os uteri had clearly opened. No rise in prostaglandin levels was recordable from induction of labour without opening of the os uteri. High primary prostaglandin levels, prior to induction of labour, and low progesterone/oestriol quotients were observed along with short-time courses of parturition. On the other hand, low prostaglandin values prior to induction of labour and slow rise during induction were recordable from protracted courses of labour.

The localization and distribution of unconjugated oestrone, oestradiol-17 beta, oestriol and progesterone were studied in normal term placentae, using subcellular fractionation and indirect immunofluorescence techniques. Radioimmunoassay of these steroids in each subcellular fraction showed that they were detectable mainly in the cytosol fraction. The efficiency of fixatives for retaining steroids in placental tissue during immunohistochemical procedures was studied in order to validate the present experimental techniques. As compared with other fixatives, glutaraldehyde solution produced minimal leakage of steroid hormones from placental tissue. Using an indirect immunofluorescence technique oestrone, oestriol and progesterone were detectable in the cytoplasm of villous syncytiotrophoblast of fixed term placentae.

During pregnancy, different protein (hCG and hPL) and steroid (progesterone, oestradiol, oestrone, oestriol) hormones are secreted. hCG, measured by RIA in maternal serum, is a first-trimester trophoblastic function test. The serum levels of hPL reveal the placental function during the two last trimesters of gestation. The main steroid hormones, produced by the foeto-placental unit, are progesterone, oestradiol and oestrone, which control placental function, and oestriol, a good index of foetal vitality.

Described in this paper is the relationship between chorionic gonadotrophin, placental lactogen, progesterone, oestradiol and oestriol in the blood of mother and embryo. The concentrations of human chorionic gonadotrophin (HCG) and human placental lactogen (HPL) in the mother's blood toward the full term of pregnancy were found to be between 300 and 800 times as high as those in foetal blood. No arteriovenous difference in concentration between the same hormones was recorded from the vessels of the umbilical cord. While the concentrations of progesterone, unconjugated oestriol, and total oestriol in the mother's blood were lower than those in foetal blood, the opposite was true for oestradiol which was lower in foetal blood. Clearly reduced levels of progesterone, unconjugated oestriol, and oestradiol but increased levels of total oestriol were recorded from the umbilical artery, as compared to the umbilical vein. The above findings are intended to encourage thinking about selective penetrability of the placenta, whenever hormone preparations are prescribed in advanced pregnancy.

Peripheral plasma concentrations of unconjugated oestradiol 17-beta, progesterone and total oestriol were measured in 21 patients presenting with 'uncomplicated' preterm labour. Serial measurements were made during intravenous treatment with ritodrine over a period of 24 h. Mean levels of unconjugated oestradiol 17-beta fell significantly during infusion with ritodrine. Changes in progesterone levels remained within the range of diurnal fluctuations normally found in uncomplicated late pregnancy. Mean total oestriol levels fell significantly, but the changes did not exceed normal variations. No correlation was found between the magnitude, the rate or the timing of changes in any of the hormones measured and the short or long term effects of ritodrine on uterine activity. Although alterations in the peripheral oestrogen concentrations may be a direct effect of beta-mimetics, it is unlikely that this mechanism is important in the inhibition of uterine activity.

Peripheral plasma levels of the biologically important hormones of pregnancy--plasma oestradiol 17 beta, plasma oestriol, plasma progesterone, human placental lactogen (hPL) and human chorionic gonadotrophin (hCG) have been measured serially in a control group of 10 normal women who delivered at term +/- three days. A second group of patients were similarly studied when admitted in premature labour and the levels compared with the control group. The levels of all hormones except human chorionic gonadotrophin increased till 37 weeks. After the 30th week, the increase of oestriol was steeper than oestradiol and hPL. The hormone profile of the maternal plasma is a good index of feto-placental function. The hPL levels which heralded the increase in endocrine function of the feto-placental unit were also elevated in premature labour, suggesting a casual relationship of significance. Levels of plasma oestradiol in premature labour were considerably higher than in the control study and suggests an endocrine basis for premature labour of hitherto unknown aetiology.

The steroid oestrogens oestradiol-17 beta, oestrone and oestradiol-17 alpha have all been adequately identified in various body fluids and tissues of cattle. There is also good evidence for the presence of oestrone sulphate. Oestriol (or similar triols) may also be present. The oestrogens found in the systemic plasma of cattle are present in milk in similar concentrations; whether their passage into milk involves metabolism by the mammary gland is uncertain. Oestrone sulphate, at least at relatively high levels of secretion, is believed to be found only in pregnant cattle and measurement of its concentration in milk is in use as a practical test for pregnancy. A close correlation has been found between the concentrations of oestradiol-17 beta in systemic plasma and milk of non-pregnant cows and levels of this oestrogen in milk may, together with those of progesterone, now be used in studies of post-partum ovarian function.

The concentration of steroid and peptide hormones in the development of the respiratory distress syndrome of the newborn has been investigated. Serum progesterone, dehydroandrostenedione sulphate (DHAS) oestradiol, oestriol, cortisol, prolactin and human placental lactogen (HPL) concentrations were measured by radioimmune assay (RIA) in samples obtained from the maternal vein and the premature newborn's umbilical artery and vein. The results were grouped according to gestational age into two groups, 28-32 and 33-36 weeks. Serum cortisol level was lower in maternal blood and both the umbilical vein and artery if the newborn subsequently developed RDS. No deviations from healthy values were encountered with any other hormone. These observations and data in the literature suggest that maturation of the fetal lung is influenced not only by maternal glucocorticoid secretion but also by the activity of the fetal adrenal cortex.

The incorporation of 14C-glucosamine into glycoproteins (GP) and glycosaminoglycans (GAG), of 3H-leucine into protein, and the hexuronic acid (HA) content of polymerized GAG was determined in incubated placental tissue. In placentae of earlier gestational age (GA), incorporation of 14C-glucosamine was 2.6 times greater than other at 38-39 weeks GA. 19 of 26 placentae at 38-39 weeks GA responded by one or more parameters when incubated with 0.5-3 microM 17 alpha-OH-progesterone (17OHP). Those which did not respond were all of earlier GA; the placental content of GAG decreased in these from 31.1 +/- 1.8 nmol HA/mg protein to 16.4 +/- 1.5 nmol in placentae of GA 38-39 weeks. In the latter, 17OHP increased GAG by 42.5% to 24.4 +/- 2.5 nmol HA/mg protein in a 2-hour incubation. Progesterone, oestriol, cortisol and testosterone were without effect. It is concluded that synthesis of placental GAG decreases toward the end of gestation, but can be increased by 17OHP specifically. This indicates that 17OHP is a biologically active steroid and might have a role in maintaining placental function.

This in vivo investigation was done to study the effects of intravaginal oestriol (E3) administration on endometrial, myometrial and vaginal tissue of normal postmenopausal women. All women received intravaginal E3- suppositoria (containing 0.5 mg E3) once a day for 3 weeks prior to hysterectomy. The medication was continued until the day of operation. At the time of operation both uterine and vaginal tissue was obtained. The receptor content in the cytosol was measured by a multiple point-dextran -coated-charcoal assay using [3H]E2 and [3H]ORG-2058 as ligands. The receptor content in the nucleus was measured by incubating purified whole nuclei in 10 nM [3H]E2 for 18 h at 0 degrees C. We have shown that under these conditions there is a total exchange of all occupied receptors. Preliminary data on 4 patients are available. Vaginal cytology clearly showed an increase of the maturation value. Oestrogen receptor concentrations in the cytosol of all three tissues studied were lower than those obtained in untreated women, suggesting nuclear transformation of the receptor as a consequence of treatment. The nuclear E2 receptor levels cannot be compared with normal women yet. Progesterone receptors in endometrial and myometrial cytosol seemed to be higher than those in untreated women, indicating effects of the treatment. In the human, vaginal progesterone receptor cannot be used as a marker for oestrogenic stimulation because only exceptionally could their presence be detected in either treated or untreated women.

Single injections of oestriol were partially effective in sensitizing the uterus to a decidual stimulus and inducing ovum-implantation in progesterone-treated spayed mice, whereas two injections (6 h apart) were fully effective. It seems that in the progestational uterus, as in the non-progestational organ, oestriol can induce a full oestrogenic response provided that its level in the target organ is maintained. It is also concluded that ovum-implantation is not triggered by some transient early effect of oestrogen, but requires about 12 h of sustained oestrogen action for its successful completion.