Maternal ACTH Research Articles

DIURNAL SALIVARY CORTISOL PATTERNS DURING PREGNANCY AND AFTER DELIVERY: RELATIONSHIP TO PLASMA CORTICOTROPHIN‐RELEASING‐HORMONE

The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.

Human corticotropin-releasing hormone during pregnancy.

Elevated irCRH levels up to 14 ng/ml were measured in 176 females in the last trimester. The highest maternal CRH levels were found in those females in whom the period from the onset of labour to full dilatation of the cervix and the time span of delivery were shortest. irCRH in amniotic fluid (120 +/- 180 pg/ml; n = 14) was in the same range as in umbilical cord plasma (233 +/- 188 pg/ml; n = 66) and 20-fold lower than in prepartal maternal plasma (5.38 +/- 4.49 ng/ml; n = 66). irCRH in maternal plasma correlated highly to irCRH in umbilical cord plasma (p less than 0.001; n = 66). After delivery irCRH disappeared from maternal plasma with a half-life of 50 minutes (n = 14). One day postpartum irCRH levels (n = 22) were undetectable. The height of the irCRH levels in the various biological fluids did not correlate to the mode or the pathological events of delivery (n = 43). Maternal ACTH levels above the normal range were encountered only in women immediately prepartal and did not correlate to the CRH levels (253 +/- 229 pg/ml; n = 66). Cortisol levels were higher in maternal plasma than in umbilical cord plasma due to elevated CBG (n = 78). Free cortisol levels were higher in the 3rd trimester than in the 1st (2.18 +/- 0.16 vs 1.16 +/- 0.73 ng/ml; n = 42). irCRH in maternal and umbilical cord plasma correlated to the hPl and estriol levels (p less than 0.001 and p less than 0.05; n = 66). We conclude that irCRH is secreted by the placenta into both maternal and fetal circulation. Though placental CRH is undistinguishable from hypothalamic CRH, the biological significance of placental CRH remains open. Our data show that placental CRH might be responsible for the changed function of the adrenal gland during pregnancy, with higher free cortisol levels in the last trimester. The extremely elevated ACTH levels during labour and delivery indicate that CRH is not the only mediator of stress-induced ACTH secretion in the regulation of the maternal hypothalamo-pituitary-adrenal axis.

Relationship between maternal and fetal corticotrophin-releasing hormone-41 and ACTH levels in human mid-trimester pregnancy

Samples of maternal blood, amniotic fluid and umbilical arterial and venous blood were collected from 11 women at 16-24 weeks of pregnancy. Corticotrophin-releasing hormone-41 (CRH-41) and ACTH were measured by immunoradiometric assay. The mean levels of ACTH were 11 pmol/l in maternal plasma, 12 pmol/l in fetal plasma and 9.7 pmol/l in amniotic fluid. The mean levels of CRH-41 were 1.6 pmol/l in maternal plasma and 0.7 pmol/l in fetal plasma. There was a positive correlation between maternal and fetal plasma CRH-41 and between maternal CRH-41 and ACTH. In fetal plasma there was a weak inverse correlation between CRH-41 and ACTH. This is the first demonstration of CRH-41 in the circulation of the mid-trimester human fetus, but on the basis of the present findings it is not possible to specify the exact source (fetal, placental or maternal).

MATERNAL, FETAL AND AMNIOTIC FLUID ACTH, CORTISOL AND PROLACTIN IN ASSOCIATION WITH MEDICAL BETA‐ADRENERGIC STIMULATION

In view of observations indicating accelerated fetal pulmonary maturation after tocolytic therapy with beta-adrenergic agonists, this study was undertaken to determine whether the phenomenon is related to enhanced maternal or fetal ACTH, cortisol or prolactin secretion. The concentrations of ACTH, cortisol and prolactin in maternal venous blood, umbilical arterial and venous blood, and amniotic fluid were similar after short-term maternal intravenous infusion of isoxsuprine, fenoterol or isotonic saline, and they did not increase in the maternal venous blood during these treatments or during long-term treatment with intravenous ritodrine. These results suggest that the accelerated fetal pulmonary maturation induced by beta-adrenergic stimulation is not mediated by ACTH, cortisol or prolactin.

Failure of severe maternal stress or ACTH during pregnancy to affect emotionality of male rat offspring: Implications of litter effects for prenatal studies

Daily maternal neck restraint, whole body restraint, hyperthermia, and ACTH treatment during the last 3rd of gestation had no reliable effect on open-field and cage-emergence behavior in male Sprague-Dawley offspring. Many of these treatments, however, produced considerable maternal pathology and evidence for maternal adrenocorticoid release. Significant litter effects were found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on emotionality in rats. Female rats showed greater activity and less defecation than males on postpubertal open-field and cage emergence tests.

Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation

Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.

ACTH LEVELS IN MATERNAL, FETAL AND NEONATAL PLASMA AFTER SHORT‐TERM PRENATAL DEXAMETHASONE THERAPY

The effect of prenatal dexamethasone therapy (12, 8 and 4 mg doses given intramuscularly on three consecutive days) on ACTH levels in maternal plasma (n=33), mixed umbilical cord plasma (n=31) and plasma from the newborn (n=29) was studied, and the results were compared with those obtained in 56 healthy parturients and 50 of their newborn. Maternal ACTH after delivery was significantly lower in the mothers treated with dexamethasone than in the control group. Cord ACTH values were similar in the two groups. ACTH levels fell during the early neonatal period, but only at 12 to 24 hours were the ACTH levels significantly lower in the dexamethasone group than in the controls. Gestational age, birth weight and the interval between the dexamethasone therapy and delivery had no significant effect on cord ACTH levels. Short-term prenatal dexamethasone therapy seemed to have very little effect on ACTH secretion in the mother, in the fetus and in the newborn.

Placental impermeability to maternal ACTH in the rabbit

Les auteurs, utilisant de l'ACTH-I125, ont étudié le problème de la perméabilité placentaire à cette hormone chez la lapine. Les résultats obtenus démontrent que l'ACTH maternelle ne passe pas au-delà de la barrière placentaire et confirment l'indépendance foetale des concentrations plasmatiques d'ACTH.

Transport of ACTH across human placenta.

ABSTRACT The concentration of ACTH in maternal antecubital venous plasma before, during and after labor and in cord plasma of newborn infants at the time of delivery were measured by radioimmunoassay, and analyzed statistically. In 7 healthy women in the 10th month of pregnancy the concentrations of plasma ACTH just before delivery were statistically higher than the levels found before the onset of labor (p < 0.001). The fetal plasma ACTH concentration was much higher than the maternal level. The difference between the maternal and fetal ACTH concentrations was statistically significant (p < 0.005). No ACTH was detected in the cord plasma of two anencephalic infants. Moreover, after ACTH infusion into 4 healthy women during labor the concentrations of ACTH in their plasma increased to about 2.2 to 10.4 times the control values, while the concentrations in the cord plasma of their newborn infants decreaseed significantly. The difference between the ACTH concentrations in infants delivered from normal women...

Maternal-fetal ACTH relationship in man.

ABSTRACT The relationship between maternal and fetal plasma ACTH concentrations were studied at the time of delivery in 9 normal women and their normal offspring, in 1 subject with Nelson's syndrome and her normal neonate and in 2 normal women and their anencephalic babies. The mean plasma ACTH concentration in the normal women was 211 pg/ml (range 93–439 pg/ml) whereas the mean fetal plasma ACTH concentration was 226 pg/ml (range 53–570 pg/ml). The correlation between the maternal and fetal ACTH concentrations was not significant. The maternal plasma ACTH concentration in the woman with Nelson's syndrome was 20 times that of her baby's. The plasma ACTH levels in the anencephalic infants were below the normal range and much lower than their respective mother's plasma ACTH concentration. These data suggest that significant transport of maternally derived ACTH to the fetus does not occur in man.

Reactiveness of Fetal Pituitary to Stressful Stimuli. Does the Maternal ACTH Cross the Placenta?

SummaryStressful stimulus in intact fetuses, but not in decapitated fetuses, caused adrenal ascorbic acid depletion. ACTH injection into decapitated fetuses was followed by considerable adrenal ascorbic acid depletion. These data support the concept that the placenta is not permeable to ACTH.

Fetal-maternal endocrine interrelations: the hypophysealadrenal system.

The observations of Ingle and Fisher (1938) and of Walaas and Walaas (1944) that adrenalectomy of pregnant rats results in hypertrophy of the fetal adrenal glands and the findings that this hypertrophy can be prevented by the administration of desoxycorticosterone (Houssay, 1945; Walaas and Walaas, 1944) raised certain questions concerning the interrelations of the fetal and maternal hypophyseal-adrenal cortical axes and the functional integrity of the fetal pituitary-adrenal system. Specifically, is the fetal adrenal hypertrophy observed following adrenalectomy of the mother engendered by (a) an increased secretion of maternal ACTH or (b) an increased secretion of ACTH from the fetal pituitary gland, or (c) both? A considerable amount of evidence (Reviewed by Jost, 1953) has been adduced to indicate that the fetal pituitary-adrenal axis is functional and exhibits many of the interrelationships described in adult animals. The suggestion has further been made (Jost, 1953; Jones, Lloyd and Wyatt, 1953)