Maternal Plasma Cortisol Research Articles

The effects of indomethacin on uterine activity and prostaglandin (PG) concentrations during labor induced by administering ACTH to fetal sheep.

To assess the importance of endogenous prostaglandins in parturition, we have examined the effects of indomethacin on maternal steroid concentrations and on the frequency and maximum amplitude of uterine contractions during delivery induced by administering adrenocorticotrophic hormone (ACTH) to fetal sheep. Uterine contractions were evaluated by measuring amniotic fluid pressure in chronically catheterized sheep, 130-days pregnant treated for 70 h with continuous infusions of intrafetal ACTH1–24, and with indomethacin or vehicle into the maternal femoral vein. Maternal plasma progesterone and estrone concentrations and fetal plasma Cortisol concentrations were estimated by radioimmunoassays (RIAs). Concentrations of prostaglandin E (PGE), PGF, and 6-oxoPGF1α (the hydrolysis product of PGI2) were measured by RIAs in myometrium, endometrium, cotyledons, amnion, and chorioallantois at different locations of the uterus. Labor was initiated after 70 h intrafetal ACTH treatment as indicated by a significant fall in maternal progesterone (P4) and rises in maternal plasma estrone (E1) and fetal plasma Cortisol concentrations, and by increased frequency and maximum amplitude of uterine contractions. indomethacin treatment had no significant effect on maternal plasma P4 or E1. Prostaglandin (PG) concentrations within uterine tissues varied with different uterine areas. However, overall, indomethacin significantly decreased concentrations of all PGs in all tissues examined, except for PGE in myometrium and endometrium. Indomethacin administration reduced the degree of cervical softening. After ACTH infusion alone there was an increase in the frequency and maximum amplitude of uterine contractions. In animals receiving concomitant indomethacin the frequency, but not the maximum amplitude of contractions, was significantly decreased. These results suggest that PGs play a role in the regulation of myometrial activity during ovine parturition, and that their action may be directed towards the modulation of the frequency of uterine contractions.

Uterine Prostaglandin Concentrations in Sheep during Late Pregnancy and Adrenocorticotropin-Induced Labor*

Concentrations of prostaglandin E (PGE), PGF, and 6-oxo-PGF1 alpha (the hydrolysis product of PGI2) were measured by RIA in different areas of myometrium, endometrium, cotyledons, amnion, and chorioallantoic membrane taken from chronically catheterized sheep. The animals were 130 days pregnant and had been treated for 70 h with continuous intrafetal infusions of either ACTH-(1-24) or saline. Maternal and fetal plasma samples were collected at 8-h intervals beginning 48 h before the start of infusion, and maternal plasma progesterone, estrone, and estradiol and fetal plasma cortisol concentrations were estimated by RIAs. As suggested by a significant fall in maternal plasma progesterone and rises in maternal plasma estrone and fetal plasma cortisol concentrations, sheep receiving intrafetal ACTH were in early labor at the time tissue samples were taken for PG determinations. For myometrium, analysis of variance indicated a significant effect of uterine area on PG concentrations. Concentrations of 6-oxo-PGF1 alpha were elevated toward the cervical end of the myometrium in ACTH-treated animals. PGF and PGE concentrations were higher at the tubal and cervical ends of the myometrium in both groups of animals. In the endometrium of treated animals, concentrations of PGE, but not PGF or 6-oxo-PGF1 alpha, were elevated significantly. For cotyledons and chorioallantois, concentrations of PGF and 6-oxo-PGF1 alpha, but not PGE, were elevated significantly in ACTH-treated animals. PG concentrations were not elevated in amnion taken from ACTH-treated animals. For both groups, the areas of highest PG concentrations were cotyledons and chorioallantois, suggesting that these may be major sites of synthesis.

Time-trend analysis of plasma 11-desoxycorticosterone, corticosterone, cortisol, and aldosterone in fetal and maternal sheep during the last 18 days of gestation

We examined the time trend effects of approaching parturition on fetal and maternal concentrations of cortisol, corticosterone, 11-desoxycorticosterone and aldosterone in eight chronically catheterized pregnant sheep preparations. Fetal plasma cortisol describes a continuously incrementing, straight log-linear function from at least 18 days prior to delivery. Fetal plasma corticosterone describes a time trend effect similar to that of fetal plasma cortisol. Fetal plasma 11-desoxycorticosterone shows no overall time trend effect except for a terminal rise beginning at approximately delivery — 2 days. Maternal plasma cortisol, corticosterone, and 11-desoxycorticosterone concentrations show no overall time trend effects except for similar terminal rises beginning at approximately delivery — 3 days. Both fetal and maternal plasma aldosterone concentrations show wide random fluctuations with no discernible time trend effects. Concentrations of fetal and maternal 11-desoxycorticosterone and aldosterone respectively do not correlate with one another ( P > 0.05) or with cortisol and corticosterone ( P > 0.10) and must therefore be regulated through different control mechanisms. Maternal cortisol, corticosterone, 11-desoxycorticosterone and aldosterone concentrations bear no apparent relationship over time to their fetal counterparts with the approach of parturition.

The relationship between maternal plasma prolactin and cortisol concentration during labor.

Abstract Maternal prolactin (PRL) and cortisol levels were measured during induced labor and 30 min following delivery in 30 normal subjects between 38 and 41 wk of gestation. A significant decline in PRL levels was accompanied by a marked rise in cortisol levels, suggesting a paradoxal suppression of PRL due to stress of labor.

Desoxycorticosterone in normal pregnancy: III. Evidence of a fetal source of desoxycorticosterone

The source of the markedly increased secretion of desoxycorticosterone (DOC) in pregnancy has not been precisely defined. Earlier studies indicated that elevated DOC does not arise from the maternal adrenal glands. The previously observed steep gradient between fetal and maternal DOC and DOC sulfate concentrations seemed to point to a fetal source. A recent study suggests that DOC may also be derived from extra-adrenal conversion of maternal progesterone. The present investigation documents a lack of synchrony between maternal diurnal plasma cortisol and DOC patterns. Not only were the previous observations of steep gradients of DOC and DOC sulfate between fetal and maternal circulations confirmed, but also the finding of extremely high urinary excretion of DOC sulfate indicated that the sulfurylated steroid passes across the placenta. A direct linear correlation was noticed between cortisol and DOC in amniotic fluid. These observations suggest that the increased DOC arises from within the fetoplacental unit but do not rule out a maternal source.

Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy

Adrenocorticotropin (ACTH) and cortisol in plasma were measured weekly from early in gestation through delivery in five women whose pregnancies were normal. During the twelfth week of pregnancy, the concentration of ACTH in plasma of blood samples obtained between 0800 and 0900 hours was 23 ± 4.6 pg/ml (mean and SEM) and rose progressively to 59 ± 16 pg/ml at 37 weeks. The levels of ACTH in plasma were significantly lower throughout pregnancy than those found in nonpregnant women. During labor and delivery, ACTH levels rose strikingly to values of 301 ± 137 pg/ml. As pregnancy advanced, the concentration of cortisol in plasma increased progressively from 149 ± 34 ng/ml (mean and SEM) at 12 weeks to 352 ± 90 ng/ml at 26 weeks' gestation but changed minimally thereafter until labor commenced, during which values of 706 ± 148 ng/ml were achieved. ACTH and cortisol secretory patterns over a 24-hour period were also investigated in one subject during each trimester of pregnancy. Diurnal variations were observed that were qualitatively similar to those seen in nonpregnant women. From the results of these studies, we conclude that ACTH levels are suppressed in plasma of normal pregnant women but are higher in late pregnancy than in early pregnancy. The rise in plasma ACTH concentrations, as pregnancy advances, in spite of increasing levels of plasma cortisol, estrogen, and progesterone, is suggestive of the possibility that a source of ACTH exists that is not subject to negative feedback control, that the clearance of free cortisol increases as pregnancy advances, or that there is an alteration in the metabolism of the ACTH precursor protein produced by the pituitary and/or placenta.

Effect of general and peridural anesthesia on the concentrations of prolactin and cortisol in maternal plasma

Comparison of the effect of general. and peridural anaesthesla on matemalprolactin cortisol concentrations in response stress of cesarean section near term revealed that surgery under general anesthesia resulted in significant augmentation of mean maternal plasma prolactin and cortisol concentrations. By contrast, surgery under peridural anaesthesia resulted in no significant increase in mean maternal plasma prolactin levels and significant but delayed increment in mean cortisol concentrations. During pregnancy near term. the prolactin and cortisol responses to surgical stress intact but modified by the type of anesthetic administered: (Am. Oestet. GYnecol. 141:483, 1981.)

Diurnal changes in maternal plasma oestrone and oestradiol at 30 to 31, 34 to 35 and 38 to 39 weeks gestational age.

Diurnal changes in the concentrations of oestrone (E1) and oestradiol (E2) in maternal peripheral plasma have been measured in samples of blood taken at one hour intervals from women at 30 to 31, 34 to 35 and 38 to 39 weeks of pregnancy. There was a significant effect of time of sampling on the plasma concentration of E1 at all stages of gestation, and circadian changes in the levels of E1 were apparent at 34 to 35 and 38 to 39 weeks. Peak values were measured around 0830 to 0930 hours, and troughs occurred between 0130 and 0530 hours. Significant effects of time of sampling on the plasma concentration of E2 were found at 34 to 35 and 38 to 39 weeks of pregnancy; night-time concentrations were lower than the peak values at 0730 to 0830 hours. The relation of these changes to the circadian rhythms in the concentrations of cortisol and oestriol in maternal plasma are discussed.

The effects of adrenalectomy in the ovine fetus.

ABSTRACTThe effects of fetal lamb adrenalectomy (Adx) on brain function, metabolism and lung development were studied in seven experiments. Thirty‐two fetal adrenalectomies were performed at gestational ages ranging from 112 to 116 days. “Indwelling” catheters were placed in maternal and fetal circulation for chronic sampling in 15 experiments. All catheterized fetuses were spontaneously aborted within 25 days postsurgery. Of 17 noncatheterized fetuses, seven (five twins and two singletons) survived to near term (136‐144 days), at which time they were studied for the effects of Adx. Maternal plasma Cortisol concentration did not differ significantly between Adx and C (control) (Adx: 16.54 ± 2.54 μg%; C: 18.1 ± 2.65 μg%). Fetal plasma cortisol concentrations were significantly lower in Adx than in C fetuses (Adx: 1.56 μg% ± 0.35 μg%; C: 9.6 ± 2.43 μg%; p < 0.025).In mitogen tests, lymphocytes from C fetuses showed responses greater in magnitude than their Adx twins. Five of the seven Adx fetuses showed immature EEG tracing in comparison with the age‐matched control (twin C or singleton C). Quantitative measurement by light microscopy revealed significantly fewer giant alveolar or type II cells in four of six Adx fetuses, as opposed to the age‐matched twin C or singleton C (p < 0.01). The relative immaturity of the brain function and lung development in the third trimester Adx fetuses probably indicates that fetal adrenal glands are important in the development of these vital organs.

PLASMA CORTISOL CONCENTRATIONS DURING CAESAREAN SECTION

The effects of extradural and general anaesthesia on the adrenocortical response to elective or emergency Caesarean section were studied in 72 patients. Maternal plasma concentrations of cortisol were measured before surgery, at delivery, and 30 and 60 min after skin incision. Umbilical vein and artery plasma cortisol concentrations at delivery were determined also. Maternal plasma cortisol concentrations in patients receiving extradural anaesthesia did not change significantly from control at any of the time intervals. In the general anaesthesia group concentrations were significantly increased from control, at 30 and 60 min after skin incision for elective Caesarean sections, and at 60 min after skin incision during emergency surgery. There were no significant differences between the mean umbilical vein and artery plasma cortisol concentrations compared within or between extradural or general anaesthesia groups. Extradural anaesthesia, in contrast to general anaesthesia, decreases the adrenocortical response to Caesarean section surgery by blocking afferent neurogenic pathways from the surgical site. The method of anaesthesia does not influence the fetal cortisol response.

Circadian rhythms in maternal plasma cortisol and estriol concentrations at 30 to 31, 34 to 35, and 38 to 39 weeks' gestational age

In order to examine the relationship between circadian rhythms in different steroids cortisol and estriol were measured by radioimmunoassay in maternal venous plasma taken at 30- to 60-minute intervals over 24 hours from nine healthy women at 30 to 31, 11 at 34 to 35 and 10 at 38 to 39 weeks' gestation. Maternal cortisol was maximal at 0730 to 0830 hours and fell significantly to its lowest concentration between 1830 and 0130 hours. At 30 to 31 and 34 to 35 weeks there was a significant circadian rhythm in estriol concentrations which was inversely related to the circadian rhythm in cortisol. At 38 to 39 weeks mean estriol concentrations were significantly higher than those at 30 to 31 and 34 to 35 weeks but there was no significant circadian pattern. We concluded that there is an inverse relationship between maternal cortisol and estriol at 30 to 31 and 34 to 35 weeks, which would be consistent with a maternal effect on fetal adrenal function. The increase in mean concentration and absence of circadian rhythm in maternal plasma estriol at term might suggest an additional positive stimulus to fetal adrenal function. The existence of patterns in maternal estriol concentrations must be taken into account in the use of sequential measurements of this hormone during the last 10 weeks of pregnancy.

Acute and chronic effects of maternal ethanol administration on the ovine maternal-fetal unit: J.C. Rose, J.W. Strandhoy and P.J. Meis. Departments of Physiology & Pharmacology and Obstetrics/Gynecology, Bowman Gray School of Medicine, Winston-Salem, NC 27103

The purpose of this study was to examine, in the pregnant ewe and its fetus, some of the physiological consequences of acute and chronic ethanol exposure. Ethanol was infused intravenously (2 g/kg/day over 2 h) to pregnant ewes from day 100 of pregnancy to term. Control animals received isocaloric infusions of 5% dextrose. Animals were pair-fed and allowed water ad lib. Maternal (n = 5) systolic, diastolic, and mean blood pressures and heart rate rose significantly by 1 h after starting ethanol, whereas fetal (n = 4) blood pressure and heart rate did not change during ethanol infusion. Maternal ethanol infusion produced a significant rise (p less than 0.01) in both fetal (n = 8) and maternal (n = 10) plasma cortisol levels. Peak blood ethanol concentration was significantly higher in the ewe (240 +/- 6 mg.dl-1, n = 7) than in the fetus (190 +/- 9 mg.dl-1, n = 6) at the end of the 2-hour infusion. Maternal rate of elimination after ethanol infusion was terminated was 40 mg.dl-1 per hour, while fetal elimination was 10 mg.dl-1 per hour. Body weights and crown-rump lengths of fetuses from 0.82 to 1.0 gestation were significantly less in ethanol-treated animals than in age-matched control animals. Fetal plasma thyroxine and triiodothyronine increments following thyrotrophin-releasing hormone administration were significantly less in alcohol-treated than in control animals. Thus, chronic exposure to ethanol during the latter part of gestation impaired fetal growth and altered fetal endocrine function in these animals.

Correlation of plasma non-conjugated oestriol and plasma cortisol in late human pregnancy.

The present study concerns the diurnal variations of free plasma oestriol and their relationship to maternal plasma cortisol in late human pregnancy. Four pregnant women volunteered for the study. According to the half-life time of oestriol blood was drawn at intervals of 30 and 60 minutes, respectively, over a period of 24 hours. Free oestriol was measured by radioimmunoassay and cortisol was quantitated by a protein binding method. All patients exhibited a circadian rhythm for free oestriol with higher values in the evening and early night (14.4 +/- 3.7 ng/ml) than in the morning (11.3 +/- 2.3 ng/ml, P less than 0.001). The course of oestriol followed plasma cortisol in a significant negative correlation (r = -0.566, P less than 0.001). During the period of low cortisol concentration oestriol levels demonstrated the phenomenon of episodic secretion. The results suggest that the maternal adrenals predominantly regulate the circadian rhythm of free oestriol by a negative feed-back action on the foetal hypothalamus.

Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma

The effect of stress during labor on the plasma concentration of cortisol, unconjugated estriol, and human chorionic somatomammotropin was studied in 15 healthy primiparous women. According to the method of pain relief the parturients were divided into two groups. One group was given continuous epidural analgesia and the other group received pethidine, diazepam, and nitrous oxide/oxygen in response to pain. In the most stressed nonepidural group there was a significant rise in the cortisol level during labor and the estriol concentration fell significantly. In the epidural group no significant changes were observed with respect to the concentration of either cortisol or estriol. These results give further support to the hypothesis that severe maternal stress may lead to a reduced concentration of estriol in maternal plasma.

In UteroRegulation of Rhesus Monkey Fetal Adrenals: Effects of Dexamethasone, Adrenocorticotropin, Thyrotropin-Releasing Hormone, Prolactin, Human Chorionic Gonadotropin, and α-Melanocyte-Stimulating Hormone on Fetal and Maternal Plasma Steroids*

In utero regulation of primate fetal adrenal glands and their role in steroidogenesis were studied between days 125-143 of gestation (term, 167 days) in chronically catheterized rhesus monkeys. Changes in fetal and maternal plasma cortisol, progesterone, estrone, estradiol, and PRL were determined in response to infusion of dexamethasone into mothers and ACTH, TRH, PRL, hCG, or α-MSH into fetuses. Significant, (P 0.05). Despite continued supp...

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.

The relationship of maternal anxiety, plasma catecholamines, and plasma cortisol to progress in labor

The relationships among maternal anxiety, selected stress-related biochemical factors, and progress in three defined phases of labor were determined for 32 married, normal, primigravid women 20 to 32 years of age. Comparisons of plasma epinephrine, norepinephrine, and cortisol in third-trimester pregnancy, during labor, and after delivery are provided. At the onset of Phase 2 of labor (3 cm. of cervical dilatation), self-reported anxiety and endogenous plasma epinephrine are significantly correlated. With the deletion of subjects to control for the effect of medications, higher epinephrine levels are significantly associated with lower uterine contractile activity at the onset of Phase 2 and with longer labor in Phase 2 (3 to 10 cm. of cervical dilatation). The relationship between epinephrine and progress in labor is explained by an adrenoreceptor theory.

STEROIDS IN THE AMNIOTIC FLUID OF THE RHESUS MONKEY (MACACA MULATTA)

Representative C21, C19 and C18 steroids have been measured in the amniotic fluid and maternal femoral plasma of rhesus monkeys during the last 50 days of pregnancy. The concentrations of cortisol, progesterone, androstenedione, oestrone sulphate all increased in amniotic fluid before spontaneous parturition. In contrast, amniotic fluid oestradiol levels remained low and unchanged, and were always less than the concentrations in the maternal plasma. The changes in progesterone, cortisol and oestrone concentrations in amniotic fluid occurred independently of significant changes in the concentration of these steroids in the maternal plasma. Betamethasone administered to monkeys after day 150 of pregnancy suppressed amniotic fluid and maternal plasma cortisol. This treatment markedly suppressed the concentration of progesterone in amniotic fluid, but did not alter its concentration in maternal plasma. It is concluded that during late pregnancy in the rhesus monkey there is an increase in the concentration of some steroids in amniotic fluid independent of alterations in their concentrations in maternal plasma. These changes could reflect an increase in foetal adrenal steroid secretion.

Fetal breathing and adaptation to maternal hemorrhage in the sheep

The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 ± 13 minutes after the beginning of maternal hemorrhage. It lasted 30 ± 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 ± 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate.

The significance of urinary free cortisol and progesterone in normal and anencephalic pregnancy

Urinary free cortisol and progesterone were determined by radioimmunoassay in 18 normal and 16 anencephalic pregnancies and urinary free cortisol levels in 9 nonpregnant women. In normal pregnancy the urinary free cortisol (46.89 +/- 34.02 mug per 24 hours) was significantly higher (P less than 0.001) than that found with anencephaly (17.19 +/- 13.20 mug per 24 hours) and 2 1/2 times (P less than 0.001) the nonpregnant value (18.47 +/- 5.44 mug per 24 hours). In 12 of the anencephalic pregnancies, urinary free cortisol levels (11.05 +/- 5.56 mug per 24 hours) were significantly lower than in nonpregnant women (P less than 0.001). Urinary progesterone levels in normal pregnancy (15.57 +/- 9.66 mug per 24 hours) and anencephaly (18.54 +/- 12.69 mug per 24 hours) were comparable. The cortisol excretion values associated with anencephaly indicate that the normal fetus contributes substantially to the maternal plasma cortisol pool. Urinary free cortisol determinations may be a useful index of fetal adrenal dysfunction.