Fetal Corticosteroid Research Articles

Effect of absent end diastolic flow velocity in the fetal umbilical artery on subsequent outcome

Sixty babies, delivered over a six and a half year period, who had absent end diastolic frequency (AEDF) in the umbilical artery, were studied. Individually matched control pregnancies for gestational...

Regulation of β 1-adrenoceptors by glucocorticoids and thyroid hormones in fetal sheep

The effects of betamethasone alone or in combination with thyroxine (T 4) on ovine fetal β-adrenoceptors were investigated at the molecular level. Ovine fetuses (126 days gestation: term = 150 days) were treated with a single ultrasound-guided intramuscular injection of 0.5 mg/kg betamethasone, betamethasone + 50 μg/kg T 4, or saline. Forty-eight h after injection, lambs were delivered by cesarean section and evaluated three h for postnatal adaptation. Myocardial β-adrenoceptor equilibrium dissociation constant ( K d) and maximal receptor density ( B max, as assessed by [ 3H]dihydroalprenolol binding, were not significantly different in drug-treated groups compared to the control group. Northern hybridization and RNase protection assays of myocardial total RNA probed with a sheep β 1-adrenoceptor riboprobe confimed no changes in expression at the level of the gene. Levels of β 1-adrenoceptor mRNA in the lung and brain were also unaffected by the treatments. Because other genes are responsive to glucocorticoids and thyroid hormones at this stage, the absence of up-regulation of β-adrenoceptor number and steady-state levels of mRNA coding for β 1-adrenoceptor following fetal corticosteroid and thyroid hormone treatment may indicate a specific, developmentally regulated repressor mechanism.

Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment

We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant-deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age.

Ontogeny and ultradian rhythms of adrenocorticotropin and cortisol in the late-gestation fetal horse

Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278-304 days gestation (term approximately 335), were catheterized and sampled daily until delivery. Mean (+/- S.E.M.) ACTH concentrations increased significantly from 159 +/- 21 to 246 +/- 42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3.1 +/- 1.0 to 13.4 +/- 3.7 ng/ml (mean +/- S.E.M.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49.5 +/- 20.5 to 16.1 +/- 2.2 ng/ml (mean +/- S.E.M.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal corticosteroid and T4 treatment effects on lung function of surfactant-treated preterm lambs.

Three groups of sheep fetuses at 125 or 126 d gestational age randomly received a single ultrasound-guided intramuscular injection of saline, 0.5 mg/kg betamethasone, or 0.5 mg/kg betamethasone plus 50 micrograms/kg thyroxine (T4). Forty-eight hours later the fetuses were delivered, treated with a pulmonary surfactant preparation, and ventilated for 3 h. Corticosteroids alone and in combination with T4 increased FRC, compliance, and lung volumes, and decreased the protein leak into the airspace. Saturated phosphatidylcholine pool sizes recovered by alveolar washing were not changed after hormone treatment. To evaluate the function of surfactant recovered from the lambs in vivo, we treated preterm rabbits at 27 d gestational age with the large-aggregate surfactant from alveolar washes. Large-aggregate surfactants and the pulmonary surfactant preparation increased compliances and maximal lung volumes relative to those in untreated preterm rabbits. Large-aggregate surfactants improved compliance more than did the pulmonary surfactant preparation. We conclude that ultrasound-guided single fetal corticosteroid treatment followed by postnatal surfactant improved postnatal lung function in preterm lambs. Addition of T4 did not augment corticosteroid effects. The function of the exogenous surfactant was improved in premature lamb lungs independently of the fetal treatment modality.

Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat

The response of pregnant rat corticosteroid binding globulin to maternal adrenalectomy was studied as a function of the stage of pregnancy. Non-pregnant or pregnant rats were deprived of their adrenal glands during 4 days. In non-pregnant animals, adrenalectomy led to undetectable corticosterone levels and to the doubling of corticosteroid binding globulin. In pregnant rats adrenalectomized at 12 days and studied at 16 days, the serum corticosterone was likewise undetectable and the corticosteroid binding globulin was doubled as compared with pregnant rats of the corresponding age. In contrast, adrenalectomy from day 14 to 18 or from day 16 to 20 did not deplete the maternal serum corticosterone and the corticosteroid binding globulin remained unchanged. Under these conditions neither fetal corticosteroid binding globulin nor fetal corticosterone were modified. However, when the pregnant rats adrenalectomized from day 16 to 20 also received an injection of 30 mg of metyrapone on days 19 and 20 in order to inhibit fetal adrenal secretion, the maternal response was again a depletion of serum corticosterone together with an increase in corticosteroid binding globulin. Under these conditions, the fetus also reacted by a fall of corticosterone and a rise of corticosteroid binding globulin. Our results suggest that the maternal response of corticosteroid binding globulin to adrenalectomy depends on the pregnancy stage inasmuch as it may be influenced by a supply of corticosterone from the fetus during late pregnancy. Moreover, they show that in this late period, fetal corticosteroid binding globulin is regulated independently.

Human fetal and adult liver metabolism of ethylmorphine: Relation to immunodetected cytochrome P-450 PCN and interactions with important fetal corticosteroids

The N-demethylation of ethylmorphine was studied in liver microsomes from human fetuses and adult patients as well as from human fetal adrenals and kidneys. Unexpectedly the reaction was catalysed at the same rate in fetal (42.3–1277.4 pmol/mg/min in 11 individuals) and adult microsomes (414–1617.8 pmol/mg/min in two individuals), which also had similar values of the apparent K m (1.50, 1.72 mM respectively) and V max (1.33,1.81 nmol/mg/min respectively) in studies of the enzyme kinetics. There was a close correlation ( r = 0.96) between the semiquantitative immunoblotting assessment of cytochrome P-450 HLp in fetal liver microsomes (with the use of a monoclonal antibody against pregnenolone-16-alpha-carbonitrile induced rat hepatic cytochrome P-450) and the catalytic activity. The fetal adrenal microsomal N-demethylation was only 11–30% of the hepatic activity when compared within three fetuses in which such a comparison was possible. No activity was measurable in the kidneys. Two drugs that are believed to be substrates of the cytochrome P-450 HLp were tested as inhibitors of the ethylmorphine N-demethylation in human fetal and adult liver microsomes and in rat liver microsomes. Midazolam was a potent inhibitor (100% at 0.4 mM) of the reaction in all specimens, whereas cyclosporin A inhibited the reaction clearly only in adult liver microsomes. Endogenous steroids of importance in the fetal circulation were also tested as inhibitors. Progesterone and dehydroepiandrosterone inhibited the reaction by 75–80% at a concentration of 0.4 mM, whereas pregnenolone and 17-alpha-hydroxy-progesterone were almost devoid of inhibitory potency. These results are of interest in the discussion about the physiological role of the human fetal cytochrome P-450 HLp which has an unprecedented relative abundance in the liver.

Transplacental stimulation of fetal lung maturation: effect of triiodothyronine in the female and male rabbit fetus.

We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.

Glucocorticoids increase the fluidity of the fetal-rat liver microsomal membrane in the perinatal period.

Dexamethasone, a synthetic glucocorticoid, was administered to pregnant rats during the last week of pregnancy in order to examine its effects on the fluidity of the developing fetal-rat liver microsomal membrane. This early prenatal exposure to dexamethasone, which preceded the natural appearance of fetal corticosteroids, markedly accelerated the normal perinatal course of fluidization of this membrane. The lipid apparent microviscosity, which was determined by measurement of fluorescence polarization, decreased in 21-days-old treated fetuses to values that were indistinguishable from those of untreated newborn rats. This dexamethasone-mediated acceleration of membrane fluidization was associated with an increase in the index of unsaturation of the fatty acyl moiety of microsomal lipids. Dexamethasone caused a significant increase in the microsomal content of polyunsaturated fatty acids (arachidonic and linoleic acid), which was accompanied by a decrease in content of monoenoic fatty acids (oleic and palmitoleic acid). This early exposure in utero to dexamethasone precociously induced the changes in fatty acid composition of fetal-rat liver microsomal lipids that normally occur between the last day of pregnancy and the first day of extra-uterine life. These results suggest that endogenous glucocorticoids play a major role in the perinatal fluidization of the rat liver microsomal membrane.

Relationships of maternal–fetal plasma steroid and amniotic fluid electrolyte levels to uterine myoelectrical activity during late gestation in sheep

Paired bipolar electrodes were implanted in the corpus and uterotubal junctions in pregnant ewes. The temporal changes in uterine myoelectrical activity were monitored in conjunction with maternal and fetal plasma steroid and amniotic fluid electrolytes to evaluate the mechanisms regulating the prepartal uterine contractions in the ewe. Increases in total uterine myoelectrical activity were significant (P < 0.001) at both uterine locations as term approached, although significant (P < 0.01) variation existed between individual animals. Significant correlations between maternal progesterone (P < 0.05) and maternal and fetal estrogens (P < 0.01) and uterine myoelectrical activity were observed. The decline in maternal progesterone to levels of 2.03 ± 0.4 ng/mL and concomitant increases in both maternal and fetal total estrogens (199.3 ± 4.7 and 262.5 ± 11.0 pg/mL, respectively) resulted in a relatively high maternal estrogen/progesterone ratio just prior to parturition and corresponded to an approximate fivefold increase in total uterine electrical activity. Fetal cortisol concentrations were not significantly correlated with uterine myoelectrical activity; however, a positive correlation (P < 0.05) between fetal cortisol and maternal estrogen/progesterone ratios was obtained. The results of this study demonstrate a direct relationship between changes in the maternal estrogen/progesterone ratios and frequency and patterns of uterine electrical signals just prior to parturition, which may be ultimately triggered by the surge in fetal corticosteroid production.

Changes in the Concentrations of Corticosteroids in the Blood of Fetal Pigs and Their Dams During Late Gestation and Labor

Corticosteroid concentrations were determined in plasma samples obtained from chronically catheterized pig fetuses and their dams during late gestation and parturition. Mean concentrations of 14-20 ng/ml were found in fetal plasma on Days -16 to -10 before delivery and these rose to 40-60 ng/ml between Day -6 and the day of delivery. During the last 8 h of fetal life levels rose rapidly and at birth averaged 168.8 +/- 35.4 ng/ml. Maternal concentrations rose slightly during the last 3 days before delivery but increased significantly during delivery itself. Considerable variation in both the time at which the rise in fetal corticosteroids occurred and the magnitude of the rise was seen both within and between litters. Chromatographic separation indicated that the rise in fetal corticosteroids was associated with increasing cortisol concentrations rather than corticosterone. The data suggest that, while mean fetal corticosteroid concentrations increase in late pregnancy, the role of adrenal maturation of individual fetuses in the initiation of the parturition process in the pig needs further investigation.

Modifications of the steroidogenic pathway during spontaneous and adrenocorticotropin-induced maturation of ovine fetal adrenal.

The studies presented herein were undertaken to discern if modifications of the steroidogenic pathway occur during ovine fetal adrenal development. Isolated adrenal cells from 120-day-old fetuses (controls), 120-day-old fetuses which were perfused for 5 days with ACTH (ACTH-treated), and newborn lambs were incubated. with 14C-labeled pregnenolone [3β-hydroxy-5-pregnen-20-one (P5)]. The time courses (30, 60, 90, and 120 min) of P5 disappearance and the formation of labeled progesterone, 11-deoxycorticosterone (21-hydroxy-4-pregnene-3,20-dione), corticosterone, 17α-hydroxypregnenolone (3β,17α-dihydroxy-5-pregnene-20-one), 17α-dihydroxyprogesterone (17α-hydroxy-4-pregnene-3-one), 11-deoxycortisol (17α,21-dihydroxy-4-pregnene-3,20-dione), and cortisol were measured. The rate of P5, disappearance from the medium was much slower in control fetuses than in ACTH-treated fetuses or newborn lambs. In control fetuses, after 2 h, only 45% of P5 had disappeared, of which more than 85% was metabolized through the 17-deoxy pathway. In ACTH-treated fetuses and newborn lambs, all P5 was metabolized by 2 h, of which about 75% was metabolized through the 17-oxy pathway. Analysis of the time course of the different metabolites indicates that the rate-limiting steps in control fetuses are the 3β-hydroxysteroid dehydrogenase/isomerase and the 17α-hydroxylase activities. In addition, there is some partial defect in 21-hydroxylating and 11β-hydroxylating systems. At the end of a 2-h incubation, the main steroid produced by control fetal adrenal cells was corticosterone, while cortisol was the main steroid produced by newborn adrenal cells. In vivo ACTH treatment of control fetuses induced a marked increase in both 3β-hydroxysteroid dehydrogenase/isomerase and 17α-hydroxylase activities, which became comparable to those in newborn lambs. The 21-hydroxylating and 11β-hydroxylating activities, however, were lower. Therefore, the rate-limiting steps of P5 metabolism by ACTH-treated fetal adrenal cells appear to be the 21- and 11β-hydroxylations. Comparison of the rates of cortisol and corticosterone formation in the presence or absence of exogenous P5 suggests that availability of P5 is another important limiting step in the biosynthesis of corticosteroids in control adrenal fetuses. This defect was partially corrected during spontaneous and ACTH-induced fetal adrenal maturation. These results, together with those reported previously show that ovine fetal maturation involves changes in the ACTH receptoradenylate cyclase complex and in the steroidogenic pathway. Furthermore, these modifications can be accelerated by exogenous ACTH.

Plasma concentrations of progesterone, oestrogens and prostaglandin F in maternal blood and corticosteroids and oestrogens in foetal blood of cows during dexamethasone-induced deliveries.

Infusing dexamethasone at rates of 0.1, 1.0 or 10 mg/day into 6 foetal calves at day 240 of gestation (2 calves per infusion rate), induced premature calving in a mean 12, 9 and 3 days respectively. Maternal plasma concentrations of progesterone, oestrone, oestradiol-17 beta and prostaglandin F or 13,14-dihydro-15-keto-prostaglandin F, and foetal plasma concentrations of oestrone, oestradiol-17 beta and corticosteroids were monitored until calving. The maternal hormone changes observed for all cows were a decline in progesterone, and a rise in both oestrogen and prostaglandin F concentrations before calving. Dexamethasone infused at a rate of 1.0 and 10.0 mg/day suppressed plasma corticosteroids in the foetus; however at 0.1 mg/day, foetal corticosteroids increased tenfold during the last 3 days before calving. At the lowest rate of infusion, dexamethasone had no effect on foetal oestrogen levels, but at rates of 1.0 and 10.0 mg/day there was a marked rise in foetal plasma levels of oestrogen.

Hormonal control of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal rat kidney.

Triamcinolone (20 microgram per fetus) administered in utero to term rat fetuses (day 21 of gestation) increases the activities of renal G-6-Pase and PEPCK. The absence (or marked decrease) of circulating corticosteroids in fetuses from adrenalectomized, metopirone-treated mothers has, however, no clear effect on the enzyme activities. Therefore, it is doubtful that corticosteroids play a role in the development of G-6-Pase and PEPCK activities during the fetal period of life. In 21-day-old fetuses entirely decapitated on day 18, both enzyme activities are lower than intact fetuses of the same litter (G-6-Pase, -48%; PEPCK, -36%). In partially decapitated fetuses, the activity of G-6-Pase remains at the control level, whereas the PEPCK activity is clearly reduced (-39%). These results strongly suggest that on the last day of gestation the hormone group of parathormone, calcitonin, or thyroxine controls the G-6-Pase activity, whereas the hypothalamo-hypophysis system is implied in the development of PEPCK activity. Parathormone (1 unit per fetus) administered to decapitated fetuses completely restores the G-6-Pase activity. Neither rat growth hormone, synacthene, nor arginine vasopressin has significant effects on the activity of PEPCK in the kidneys of decapitated fetuses. The administration of 0.5 mumole of dibutyryl-cAMP or cyclic adenosine 3':5'-monophosphate (cAMP) to decapitated fetuses completely restores the activity of renal PEPCK, suggesting that the development PEPCK is controlled by cAMP-dependent hormone. The same dose of dibutyryl-cAMP has no effect on the activity of G-6-Pase; cAMP produces a slight but significant increase of this enzyme activity.

11 beta-Hydroxyteroid dehydrogenase activity (E.C. 1.1.1.146) in human placenta and decidua.

Abstract 11β-Hydroxysteroid dehydrogenase activity (E.C. 1.1.1.146) was studied in homogenates of placenta, fetal membranes and decidua obtained at term, using cortisol and cortisone as substrates. For activity in the direction cortisol to cortisone, the distribution of enzyme was choriodecidua > placenta. While choriodecidua catalysed the conversion in both directions, cortisone reduction was negligible in placenta. Amnion contained no measurable enzyme, using either substrate. The activity in the choriodecidua was thought to be of decidual rather than chorionic origin. In both decidua and placenta, the enzyme was localised by subcellular fractionation in the microsomal fraction, and microsomal fractions were used to study the dependence of activity on pH, substrate and enzyme concentration and the inhibitory effect of other steroids. Data on the K M values for cortisol and the inhibition of the enzyme by some steroids, notably androgens, suggest that the enzymes in decidua and placenta may be different. The findings are discussed in relation to the possible role of the enzyme in the control of fetal corticosteroid concentrations.

The pharmacologic inhibition of premature labor.

Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly.

PARTURITION IN GOATS: STUDIES ON THE INTERACTIONS BETWEEN THE FOETUS, PLACENTA, PROSTAGLANDIN F AND PROGESTERONE BEFORE PARTURITION, AT TERM OR AT PARTURITION INDUCED PREMATURELY BY CORTICOTROPHIN INFUSION OF THE FOETUS

Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occured when progesterone declined to low levels, probably reflecting in the course of labour. The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteoid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently. The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life.

Foetal and maternal hormonal changes preceding normal bovine parturition.

Successful chronic cannulation of the foetal posterior vena cava and maternal utero-ovarian and jugular veins in five Jersey cows between days 240 and 260 of gestation enabled changes in plasma hormone levels preceding calving to be monitored. All cows delivered live calves within the expected range of gestation for the breed. Corticosteroids were assayed by competitive protein-binding and prostaglandin F, progesterone, oestrone and oestradiol-17beta by radioimmunoassay. Foetal corticosteroids rose slowly from 5.0 +/- 0.7 ng/ml at 20 days to 9.3 +/- 3.0 ng/ml at 10 days before term, then progressively increased to a mean of 74 ng/ml, though higher concentrations occurred following surgery. Foetal oestrone and oestradiol-17beta concentrations were both less than 50 pg/ml and showed little change toward term. The maternal utero-ovarian oestrogens increased slowly from 20 to 10 days pre-partum and then rose more rapidly reaching peak levels (2.9 +/- 0.6 ng/ml for oestrone and 1.4 +/- 0.3 ng/ml for oestradiol-17beta) 1 to 4 days before delivery. Maternal progesterone concentrations fell towards term, with a rapid decrease over the last 36-48 h before calving when they gradually increased until the last 24 h where was a dramatic rise, reaching peak levels (5.7 +/- 0.6 ng/ml) during labour.

Rapid increase of foetal corticosteroids after prostaglandin E2.

MATURATION of the foetal hypothalamo-hypophyseal-adrenal axis appears to be involved in the initiation of parturition in several species1,2, but the limiting determinant of this maturational process has not yet been identified. In sheep, an increase in the plasma cortisol concentration of the foetus has been observed before parturition3,4 but it has been demonstrated that this increase is not preceded by an elevation in plasma ACTH5. It has been suggested that there is a maturation of the foetal adrenal responsiveness to ACTH stimulation6,7 and perhaps activation of those enzymes specifically associated with cortisol production8. Recently we have shown that a primary prostaglandin, prostaglandin E2 (PGE2), is present in the plasma of the foetal lamb and that its concentration increases during late pregnancy9. Here we examine the possibility that prostaglandins may be an essential factor in the stimulation of corticosteroid production in the foetus and report a very rapid increase in foetal corticosteroids during PGES infusion into the common carotoid artery of foetal lambs.

Fetal and neonatal breathing movements in man after betamethasone

Nineteen women in the last trimester of pregnancy were treated with betamethasone 12 mg daily for three consecutive days. The fetal breathing movements were monitored by an ultrasonic method before and after the treatment and the patterns of movements were compared to those in controls. In seven treated cases the recording of breathing was performed also in the neonatal period. Betamethasone in the given dose, which causes pronounced alterations in the fetal corticosteroid balance, does not influence the pattern of breathing movements in the fetus and newborn. Although corticosteroids are known to affect several functions of CNS, the maturation of mechanisms regulating breathing movements in the perinatal period is apparently not accelerated by betamethasone.