Action of sex steroid hormones on temperature-induced sex determination in the snapping turtle (Chelydra serpentina)

Administration of exogenous estradiol benzoate (EB) or an estrogen agonist, R2858, into eggs of snapping turtles caused all embryos incubated at male-producing temperatures to develop as females, whereas testosterone propionate (TP) caused 42% of the embryos to develop as females. Some of the embryos treated with EB, R2858, or TP also had hypertrophied oviducts. Neither dihydrotestosterone (DHT) nor cholesterol had any apparent effect on the sex determination of embryos incubated at male-producing temperatures. Injections of TP, DHT, the androgen agonist R1881, or cholesterol had no apparent effect on sex determination of embryos incubated at female-producing temperatures. Administration of estradiol antiserum or testosterone antiserum resulted in some individuals having undifferentiated or ambiguous gonads. Although both exogenous estrogens and androgens can induce embryonic gonads to develop as ovaries, the findings of this study indicate that estrogen is the female-inducing hormone and that androgens may feminize gonads via aromatization to estrogen. Furthermore, the results of the antisera injection suggest that endogenous steroid hormones may have a natural role in gonadal differentiation of reptiles with environmental sex determination.     

Role of the serum estrogen-binding protein in the control of tissue estradiol levels during postnatal development of the female rat.

The role of the serum estrogen-binding protein (EBP) in the control of tissue estradiol levels during postnatal development of the female rat was examined. The estradiol-binding capacity of serum from the 1-day-old rats far exceeded the physiological level of estradiol in serum. The binding capacity decreased exponentially during the first 5 weeks of life to reach the low adult level at about the time of vaginal opening on day 37. From these observations one would predict that EBP would bind estradiol in the serum of the neonate, thereby preventing tissue uptake of the hormone. As the levels of EBP decline with advancing age, there should be a corresponding shift in the distribution of estradiol from serum to tissues. We have taken in vivo and in vitro approaches to evaluate these proposals. Female rats of various ages (1 day to 1 yr old) were sacrificed 1 h after [3H]estradiol injection and the radioactivity in serum and tissues was determined. During the first 11 days of life, the concentration of [3H]estradiol in serum was greater than the concentration of this hormone in estrogen-sensitive (uterus) and insensitive (lung, cerebral cortex, and diaphragm) tissues. Tissue to serum ratios of [3H]estradiol increased progressively between 13-34 days and then plateaued at about the time of puberty (37 days of age) at levels which were 50- to 150-fold greater than those observed in the neonate. The increase in tissue to serum ratios of [3H]estradiol during postnatal development probably resulted from the decline in serum EBP, since injection of neonatal serum into 28-day-old rats reduced tissue to serum ratios of [3H]estradiol to levels which were similar to those observed in 16-day-old animals. To determine the effects of EBP on uterine uptake of estradiol in vitro, uteri from 21-day-old rats were incubated with [3H]estradiol and serum obtained from rats of various ages. As the concentration of serum EBP declined with advancing serum donor age, there was a corresponding increase in the uterine uptake of [3H]estradiol. These results suggest that the decline in EBP is responsible for the progressive increase in tissue to serum ratios of estradiol during the first 5 weeks of life. It is suggested that the increase in tissue to serum ratios of estradiol between days 13-37 postpartum is an important factor in the initiation of estrogenic events during postnatal sexual maturation in the female rat.     

EBP50 inhibits the anti-mitogenic action of the parathyroid hormone type 1 receptor in vascular smooth muscle cells

Parathyroid hormone-related protein (PTHrP) and the parathyroid hormone type 1 receptor (PTH1R) are important regulators of vascular remodeling. PTHrP expression is associated to increased proliferation of vascular smooth muscle cells (VSMC). In contrast, signaling via the PTH1R inhibits cell growth. The mechanisms regulating the dual effect of PTHrP and PTH1R on VSMC proliferation are only partially understood. In this study we examined the role of the adaptor protein ezrin–radixin–moesin-binding phosphoprotein (EBP50) on PTH1R expression, trafficking, signaling and control of A10 cell proliferation. In normal rat vascular tissues, EBP50 was restricted to the endothelium with little expression in VSMC. EBP50 expression significantly increased in VSMC following angioplasty in parallel with PTHrP. Interestingly, PTHrP was able to induce EBP50 expression. In the clonal rat aortic smooth muscle cell line A10, EBP50 increased the recruitment of PTH1R to the cell membrane and delayed its internalization in response to PTHrP(1–36). This effect required an intact C-terminal motif in the PTH1R. In naïve A10 cells, PTHrP(1–36) stimulated cAMP production but not intracellular calcium release. In contrast, PTHrP(1–36) induced both cAMP and calcium signaling in A10 cells over-expressing EBP50. Finally, EBP50 attenuated the induction of p27^kip1 and the anti-proliferative effect of PTHrP(1–36). In summary, this study demonstrates the dynamic expression of EBP50 in vessels following injury and the effects of EBP50 on PTH1R function in VSMC. These findings highlight one of the mechanisms leading to increased VSMC proliferation and have important implication in the understanding of the molecular events leading to restenosis.     

Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus

The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.     

In vivo and in vitro binding of [3H]estradiol in brain and pituitary of Mongolian gerbils, Meriones unguiculatus.

Following injection of [³H]estradiol in ovariectomized gerbils, the highest concentration of radioactivity was found in cell nuclei from the pituitary, followed by preoptic area, hypothalamus, amygdala, and midbrain, with very low levels in the olfactory bulbs and cerebral cortex. Cell nuclear binding was significantly reduced by pretreatment with unlabeled estradiol or nafoxidine but not by progesterone, 5α-dihydrotestosterone, or cortisol. The time course of estradiol binding in whole homogenate and cell nuclear fractions of brain and pituitary was determined by sacrificing animals 0.25, 1, 3, 6, or 12 hr after injection of [³H]estradiol and measuring hormone uptake into the respective cell components. While whole homogenate radioactivity was highest at 0.25 hr, cell nuclear uptake peaked at 1 hr. Radioactivity was still present in cell nuclei from pituitary, hypothalamus-preoptic area, and amygdala 12 hr after [³H]estradiol injection, although at a level only 2% of 1-hr peak values.Macromolecular binding of [³H]estradiol was found in the cytoplasmic fraction of pooled hypothalamus-preoptic area-amygdala. Scatchard analysis of this in vitro binding indicated a K_d of 5.0 × 10⁻¹⁰M. This binding was inhibited more by unlabeled estradiol or the synthetic estrogen, R2858, than by 5α-dihydrotestosterone, progesterone, or cortisol. Pronase almost totally inhibited binding, while DNase and RNase had little effect. The data indicate that the estradiol binding in female gerbil brain and pituitary is similar to that of other species previously studied, although some species differences were found.     

Characterization of an estrogen-binding protein in the yeast Candida albicans

An estrogen-binding protein (EBP) has been identified and characterized in the cytosol of the pathogenic yeast Candida albicans. Binding of [3H]estradiol was found to be optimal at pH 7.4 in the presence of 0.3 M KCl and was linearly related to protein concentration. Binding was very rapid, reaching maximal levels in about 30 min, and was reversible with a dissociation rate constant of 13.2 +/- 1.7 x 10(-4) sec-1. EBP binding was destroyed by treatment with proteolytic enzymes and by high temperatures. Scatchard analysis of the [3H]estradiol equilibrium binding data of C. albicans (strain stn-1) yielded an apparent dissociation constant of 12.3 +/- 2.1 nM and a maximal binding capacity of 753 +/- 145 fmol/mg protein. Binding competition experiments showed very high specificity and stereoselectivity of EBP, demonstrating the following order of potency in displacing [3H]estradiol: 17 beta-estradiol greater than estrone greater than estriol greater than 17 alpha-estradiol. Negligible competitive potency was found for other mammalian steroid hormones, diethylstilbestrol, tamoxifen, or fungal hormones. The abundance of EBP was 4- to 10-fold higher during the early logarithmic growth phase of yeast cells than during the stationary phase. The molecular size of EBP, measured by Sephacryl S-200 gel exclusion chromatography, yielded a Stokes radius of approximately 29 A. Sucrose density gradient sedimentation showed a sedimentation coefficient (S2020,W) of 4, with no ionic dependent aggregation of the [3H]estradiol-EBP complex. The apparent mol wt of the EBP is approximately 46,000, with an axial ratio of 1, indicating the symmetrical shape of the molecule. In summary, in addition to the previously described corticosterone-binding protein, a separate high affinity, stereospecific, estrogen-selective binder has been demonstrated in the cytosol of C. albicans.     

Maturation of the inhibitory feedback action of oestrogen on follicle-stimulating hormone secretion in the immature female rat: a role for alpha-foetoprotein.

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11 beta-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0.00015 microgram R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0.05 to 0.01 microgram/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.     

The characteristics of the estrogen-binding protein from the pancreas of female and male rats

Hormone-binding and some other physicochemical properties of an estrogen-binding protein (EBP) from the female and male rat pancreas in partially purified specimens were studied. Kinetic parameters of the hormone-protein interaction were found to be the same for males and females. However the concentration of binding sites for estradiol in females was higher than that in males. The female and male EBP exhibited nearly the same specificity for hormonal compounds except for some estrogens and androgens, whose competitive efficiency was higher in males. These sex differences were found not to be ascribed to diverse intensity of hormonal metabolism during incubation with male and female EBP specimens. The data obtained are suggestive of sex differentiation in the quantity and/or quality of low molecular "accessory" factor modifying EBP hormone-binding properties.     

Daily hormonal changes in the maternal, fetal, and amniotic fluid compartments before parturition in a primate species

The daily hormonal fluctuations that occur simultaneously in the fetus, mother, and amniotic fluid during late gestation and before preterm parturition were studied in long term catheterized rhesus macaques. Blood and amniotic fluid samples were collected twice daily and analyzed by RIA for estrone, estradiol, dehydroepiandrosterone sulfate (DHEAS), progesterone, cortisol, and prostaglandin F2 alpha metabolite (PGFM). Vaginal delivery in monkeys with live fetuses was preceded by rising concentrations of DHEAS in fetal, but not maternal, blood. Parallel increases in fetal plasma estrone, maternal plasma estrone and estradiol, and amniotic fluid estrone preceded the rise in amniotic fluid PGFM (P less than 0.005, by analysis of variance). Cortisol levels remained stable in maternal blood and amniotic fluid, but increased before delivery in fetal blood. Nocturnal progesterone peaks in both fetal and maternal blood increased progressively in magnitude in fetuses before parturition. Rising concentrations of fetal DHEAS, estrone, and progesterone indicated an increase in adrenal activity before parturition in the rhesus fetus. PG production, reflected in amniotic fluid PGFM concentrations, was temporally related to increasing amniotic fluid concentrations of estrone. Although progesterone withdrawal may occur at a local tissue level, parturition occurred without an apparent decrease in circulating maternal, circulating fetal, or amniotic fluid progesterone concentrations.     

Plasma Levels of Immunoreactive Melatonin, Estradiol, Progesterone, Follicle Stimulating Hormone, and β-Human Chorionic Gonadotropin During Pregnancy and Shortly After Parturition in Humans

Plasma concentrations of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone (FSH), and beta-human chorionic gonadotropin (beta hCG) were studied between 1000 and 1230 h in 105 Chinese females during six periods of normal pregnancy and 1-5 min after normal delivery. We have also examined the midday levels of immunoreactive melatonin in the cord blood of fetuses and plasma collected 1-5 min after and 24 h after delivery from their mothers. Concentrations of hormone immunoreactivities were determined by radioimmunoassay, and distinct fluctuations of all hormones were recorded during pregnancy. In the pregnant females, there were significant negative correlations between melatonin and estradiol, melatonin and progesterone, beta hCG and progesterone, and beta hCG and estradiol, and positive correlations between melatonin and FSH and progesterone and estradiol. Furthermore, plasma melatonin levels in the cord blood demonstrated no sex difference and were significantly lower than and correlated positively with the levels in their mothers. Our results suggest that sex steroids may inhibit and FSH may potentiate circulating melatonin levels in gravid women; changes in the levels of melatonin during pregnancy may affect the in utero development of the human embryo; and circulating melatonin in the mother may be the major source of blood melatonin in the fetus before parturition.     

Perinatal consequences of maternal-fetal Rh blood group interaction in diabetic pregnancy: a nonimmunological perspective

BACKGROUND: The recent discoveries about the structure of Rh protein that suggest a transport function and the recent observations of a positive correlation between Rh(D) protein and glycosylated hemoglobin levels in non-insulin-dependent diabetes mellitus prompted us to review our data on diabetic pregnancy to evaluate the perinatal consequences of maternal-fetal Rh blood group interactions in a metabolic perspective. SUBJECTS AND METHODS: One hundred thirty-two women with gestational diabetes and 120 women with preexisting insulin-dependent diabetes mellitus were examined. Three hundred eighty-seven consecutive nondiabetic puerperae from the same population were considered control subjects. RESULTS: In both gestational and insulin-dependent diabetes mellitus, an increased proportion of mother Rh(+)/newborn Rh(-) and a decreased proportion of mother Rh(-)/newborn Rh(+) joint phenotype has been observed. No deviation has been observed for joint phenotypes in which mother and newborn are similar [ie, Rh(+)/Rh(+) and Rh(-)/Rh(-)]. In the situation of mother Rh(+)/newborn Rh(-), there is a relatively lower rate of fetal loss and a decreased tendency to high birth weight. On the contrary, in pairs mother Rh(-)/newborn Rh(+) the fetus shows an increase of fetal loss and of tendency to high birth weight. CONCLUSIONS: The results are compatible with the hypothesis that when the density of Rh protein in the mother is higher than that in the fetus, the conceptus is relatively protected against the toxic effect of glucose. In the opposite genotypic combination (ie, density of Rh protein higher in the fetus than in the mother), the fetus is relatively more susceptible to these effects.     

Effect of estrogen on pituitary peptide-induced dehydroepiandrosterone secretion in the baboon fetus at midgestation

We have previously shown that ACTH and PRL stimulate baboon fetal adrenal dehydroepiandrosterone (DHA) production both in vitro and in vivo and that estrogen diminishes the responsivity of the adrenal to tropic peptides in vitro. In the present study we determined the effects of increasing placental estrogen production by the administration of androstenedione at midgestation on DHA production by the baboon fetus in vivo. Pregnant baboons were untreated (n = 8) or treated (n = 9) with increasing numbers of androstenedione implants inserted in the mother at 8-day intervals between days 70-100 of gestation (term = day 184). On day 100, the fetuses were exteriorized, and a constant infusion of saline (0.1 ml/min) was initiated via a catheter inserted into a femoral vein of the fetus. At 40 min, a bolus injection of either 30 nmol ACTH or 40 nmol ovine PRL was administered to fetuses. ACTH or PRL (0.2 nmol/min.0.1 ml saline) were then infused for an additional 25 min. The concentrations of serum estradiol (E2) in the uterine vein (20.2 +/- 1.5 ng/ml; mean +/- SE) and estrone (E1) in umbilical vein (11.9 +/- 3.1 ng/ml) of androstenedione-treated baboons were 2-fold greater (P less than 0.05) than respective values in untreated baboons. Baseline concentrations of DHA in the femoral vein of the fetus were similar in all treatment groups (overall mean, 120 +/- 20 ng/ml) and greater (P less than 0.05) than values (27 +/- 3) in the mother. In untreated control baboons, basal DHA concentrations in the fetus were increased (P less than 0.05) by 69 +/- 17% and 94 +/- 29% after fetal injection of ACTH (n = 4) or PRL (n = 4), respectively. In contrast, neither PRL (n = 5) nor ACTH (n = 4) had any effect on serum DHA when injected into androstenedione-treated baboons. Regardless of treatment, injection of ACTH or PRL into the fetus had no effect on DHA concentrations in the mother. Collectively, these findings indicate that the ability of the fetal adrenal to increase DHA production in response to an acute infusion of ACTH or PRL was abolished in baboons in which placental estrogen production was increased prematurely at midgestation. Therefore, we suggest that during the second half of gestation in the baboon a regulatory system may exist in utero, in which there is feedback control of the placental product estrogen on the formation of the fetal adrenal precursor DHA.     

Prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) applies to a group of inherited disorders caused by an enzyme deficiency in steroid biosynthesis. The most common form of CAH is 21-hydroxylase deficiency (21-OHD), which in its severe form can cause genital ambiguity in females. Affected females experience virilization both physically and psychologically. Steroid 21-OHD can be diagnosed in utero through molecular genetic analysis of fetal DNA. Appropriate prenatal treatment by dexamethasone administration to the at-risk pregnant mother is effective in reducing genital virilization in the fetus, thus avoiding unnecessary genitoplasty in affected females. Current data from large human studies show that prenatal diagnosis and treatment are safe in the short term for both the fetus and the mother. Preliminary data from long-term studies support these results.     

Effects of oestradiol-17beta, oestradiol benzoate and the synthetic oestrogen RU 2858 on sexual differentiation in the neonatal female rat.

Groups of neonatal female rats were treated for the first 5 days of life with oestradiol-17beta, oestradiol benzoate or a synthetic oestrogen, 11beta-methoxy-17-ethynyl-1,3,5(10)-oestratriene-3,17beta-diol (RU 2858), in daily doses ranging from 0-5 to 1000 ng. Oestradiol-17beta had no effect on adult ovarian cyclicity or sexual receptivity after ovariectomy and oestrogen+ progesterone treatment. Ovarian cyclicity was prevented by 100 ng or more oestradiol benzoate/day, and by all doses of RU 2858. Only rats receiving 50 ng oestradiol benzoate/day or 0-5 ng RU 2858/day showed normal receptivity. The defeminizing action of RU 2858 was at least 100 times greater than that of oestradiol benzoate; it is suggested that this greater potency is due to the low affinity of RU 2858 for the oestradiol-binding protein in the plasma of neonatal rats. These results indicate that defeminization of the neonatal rat brain can be induced by physiological amounts of oestrogen, and are discussed with reference to the action of testosterone.     

Desensitization of brain opiate receptor mechanisms by gonadal steroid treatments that stimulate luteinizing hormone secretion

We studied the effects of two ovarian steroid treatments that induce proestrous-like surges in LH secretion on responsiveness to morphine sulfate (MS), as measured by induced hypothermic, antinociceptive, behavioral, and LH secretory changes. Ovariectomized rats received no steroids (OVX), 7.5 micrograms estradiol benzoate 2 days before the experiment (EB), or EB and then 5 mg progesterone 48 h later (EBP). MS administration coincided with the steroid-induced LH hypersecretion that occurs in the EB and EBP rats at 1530-1630 h. Serum LH concentrations were determined 30 min after administration of MS. In OVX and EB rats, MS caused a dose-dependent decrease in serum LH, but even 20 mg/kg MS did not alter serum LH during the EBP-induced LH surge. Brain-mediated morphine-induced analgesia was evaluated in the three steroid treatment groups from measurement of latency to pawlick on a hot plate. EB and EBP rats were less responsive than OVX rats to MS-induced antinociception. EB and EBP rats were also less responsive than OVX animals to the spinal cord-mediated analgesia due to MS, as calculated by tail-flick latency. MS-induced hypothermia revealed a responsiveness order of OVX greater than EB greater than EBP. Whereas MS caused a dose-dependent reduction in locomotor activity in OVX and EB rats, EBP rats showed marked hyperactivity at low MS doses and were less responsive to the suppression of locomotor activity at higher doses. These marked steroid-induced changes in MS responsiveness could not be explained by altered pharmacokinetic disposition of morphine. These data indicate that treatment with EBP, which stimulates a preovulatory-like LH surge, decreases the ability of MS to induce hypothermic, antinociceptive, and behavioral responses and abolishes its capacity to suppress LH release. These effects of gonadal steroids were not observed before the LH surge, which suggests that this surge is linked to the decline in MS sensitivity. Further, the diminished response to MS appears to be a function of the magnitude of the LH surge.     

Clinical counterpoint: the physiology of placental lactogen in human pregnancy.

In summary, current evidence strongly suggests that PL may play a pivotal role during pregnancy, acting through distinct PL receptors to regulate and coordinate growth and metabolism in the mother and fetus. In early and midgestation, PL may be secreted preferentially into the fetal circulation, exerting growth-promoting effects at a time when the rate of linear growth of the fetus is maximal. Subsequently, during the latter half of pregnancy, the metabolic actions of PL in the mother and fetus may predominate, ensuring the optimal supply of nutrients to the fetus and utilization of the nutrients by fetal tissues. It therefore appears that PL affects fetal growth both by exerting effects on the fetus and the mother. Although hPL acts as "growth hormone of pregnancy," the regulation of the synthesis and secretion of hPL appears to be markedly different than that of GH.     

Regulation of membrane-associated prostaglandin E2 synthase 1 in pregnant sheep intrauterine tissues by glucocorticoid and estradiol

This study was designed to determine the regulatory effect of glucocorticoid and estradiol on expression of ovine intrauterine membrane-associated prostaglandin E(2) synthase 1 (mPTGES1) in late gestation and at labor. For gestational and labor groups, 16 pregnant ewes from 95-147 d gestational age (dGA) and four pregnant ewes at spontaneous term labor were used. The fetal glucocorticoid group, 14 pregnant ewes at 123-125 dGA with fetuses, was divided into the following groups: after sham adrenalectomy (n = 5), adrenalectomy (n = 4), and adrenalectomy with fetal cortisol replacement to late gestation levels (n = 5). For the maternal glucocorticoid group, nine pregnant ewes were treated with saline (n = 4) and three courses of maternal dexamethasone (n = 5). For the estradiol group, 10 pregnant ewes at 119-121 dGA were treated with sesame oil (n = 5) or estradiol (n = 5) to produce labor levels of estradiol in maternal plasma. Endometrial, myometrial, and placental mRNA and proteins were analyzed by Northern and Western blot and immunocytochemistry for mPTGES1. Data were analyzed by Student's t test and ANOVA. There was a significant increase of placental mPTGES1 in late gestation. Glucocorticoids, given to the mother or fetus, significantly stimulated mPTGES1 in placenta. mPTGES1 was elevated only in the endometrium during spontaneous term labor and after estradiol treatment. The mPTGES1 was localized in the myometrial smooth muscle cells, endometrial stromal cells, and placental trophoblast cells. Our study suggested that increased expression of placental mPTGES1 throughout late gestation might result from the increased fetal and maternal circulating glucocorticoids, whereas elevated maternal plasma estradiol concentration might be responsible for the induced mPTGES1 expression in the endometrium during labor.     

Maternal Immunosuppression and Cytomegalovirus Infection of the Fetus*,†

Summary: Maternal immunosuppression and cytomegalovirus infection of the fetus. K. Hayes, G. Symington and I. R. Mackay, Aust. N.Z. J. Med., 1979. 9, pp. 430–433. Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended.     

Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery

The aim of this study was to evaluate the effect of vaginal delivery on both ACTH and catecholamines (DA, NE, E) secretion in the mother, the fetus (umbilical artery) and the newborn. Blood samples were obtained from 19 normal pregnant women and the corresponding umbilical cords, and from the newborns. Seventeen normal nonpregnant women, matched for age and parity, were also included in the study as "nonpregnant controls". The results demonstrate that in the mother, plasma catecholamines (CA) concentrations during labor and delivery are elevated above the values reported for normal nonpregnant women and there is a predominant E response. The concentrations of CA in umbilical arteries are very high compared to those in the corresponding mother and they fall rapidly after birth. Unlike that in the mother, the predominant CA response to parturition in the fetus and newborn infant is NE. The extraction rate of DA, NE and E from placenta is approximately 60%. The peripheral plasma levels of ACTH in pregnant women during labor are twice and 10 times as high as those observed in the corresponding umbilical arteries and in nonpregnant women respectively. At delivery they increase further. No significant differences are found between the values measured in the arterial cord blood and those in the venous cord blood and in the newborns. A way of explaining the prevalence of E and the higher ACTH/E ratio found in the mother in comparison with the fetus could be that in the mother the stress response to parturition is regulated mainly by the pituitary-adrenal axis, whereas in the fetus there is a prevalent stimulation of the sympathetic nervous system.