Fetal Plasma Cortisol Concentrations Research Articles

Regulation of lung liquid secretion by arginine vasopressin in fetal sheep

We have investigated the influence of gestational age on the inhibition of fetal lung liquid secretion by arginine vasopressin (AVP). In eight fetal sheep, lung liquid secretion rates were measured before and during infusion of AVP (300 mu.kg-1.h-1) at gestational ages between 110 and 148 days. During infusions, the concentration of AVP in fetal plasma increased from less than 8.7 +/- 0.2 pg/ml to 848.7 +/- 75.1 pg/ml. Fetal plasma epinephrine concentrations were not altered during AVP infusion. Infusions of AVP had no effect on fetal lung secretion before 135 days of gestation; they caused a 40.8% inhibition between 136 and 140 days, and at ages greater than 140 days induced an inhibition of 78.4%. In two ewes during labor, AVP infusion caused either a complete inhibition of secretion or reabsorption of lung liquid. The inhibitory effect of AVP increased in an exponential-like fashion with increasing gestational age and appeared to parallel the preparturient rise in fetal plasma cortisol concentrations. Our results indicate that AVP may be involved in the clearance of lung liquid at term and that AVP is unlikely to mediate the inhibitory effect of fetal asphyxia on lung liquid secretion, at least until after 135 days of gestation.

Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep.

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of γ 2 or γ 2Melanocyte Stimulating Hormone on steroidogenesis in the fetal sheep during late gestation

We have measured circulating concentrations of γ 3 Melanocyte Stimulating Hormone (MSH) in fetal sheep between 111 and 145 days gestation. There was no significant effect of gestational age on the fetal plasma concentrations of γ 3MSH throughout this period. We have examined the role of γ-MSH related peptides in the control of fetal adrenal steroidogenesis and found no significant change in fetal plasma cortisol or pregnenolone concentrations during a 60–72h infusion of saline, γ 2MSH or γ 2MSH in sheep between 130 and 130 days gestation. Therefore although we have demonstrated the presence of γMSH related peptides in fetal sheep plasma during late gestation we have failed to demonstrate a role for γ 3 or γ 2MSH in the changes in fetal steroid concentrations which occur prepartum.

Are fetal adrenocorticotropic hormone and renin secretion suppressed by maternal cortisol secretion?

Previous studies from this laboratory have demonstrated that intravenous infusions of hydrocortisone (cortisol) into fetal sheep at rates that produce plasma concentrations achieved during fetal stress inhibit fetal adrenocorticotropic hormone (ACTH) and renin secretion. The present study was designed to test for inhibition of fetal renin and ACTH after maternal adrenal secretion of cortisol. ACTH-(1-24) or saline infusion into 12 pregnant ewes (120-132 days gestation) at rates of 0, 1, 5, or 20 ng ACTH.kg-1.min-1 for 5 h produced dose-related increases in maternal plasma ACTH and cortisol concentrations and fetal plasma cortisol concentration. In the 20-ng.kg-1.min-1 group, increases in fetal plasma cortisol of 8.0 ng/ml (to 24.3 +/- 3.7 ng/ml) did not suppress basal fetal plasma renin activity. One hour after the end of the maternal vehicle or ACTH infusion, fetal ACTH secretion was stimulated by fetal intravenous infusion of sodium nitroprusside. In the 0-, 1-, and 5-ng.kg-1.min-1 groups, fetal ACTH responses to nitroprusside were suppressed in animals infused with ACTH. Together, these results indicate that the maternal adrenal secretion of cortisol inhibits stimulated secretion of ACTH but not renin in 120- to 132-day-gestation fetal sheep.

Insensitivity of near-term fetal sheep to cortisol: possible relation to the control of parturition.

In ruminants, parturition is stimulated by increased cortisol secretion by the fetal adrenal in the last few days of fetal life. Before this preparturient surge in fetal plasma cortisol, fetal ACTH and renin secretion are suppressed by small physiological increases in the fetal plasma cortisol concentration. The purpose of this study was to investigate the possibility that the sensitivity of ACTH and renin to cortisol inhibition is reduced at term. Fetal sheep, chronically catheterized at least 4 days before the first experiment, were subjected to iv infusion of cortisol at rates of 0 (n = 5), 1 (n = 4), 2 (n = 4), 5 (n = 5), and 10 (n = 5) micrograms/min for 5 h. One hour after the end of the cortisol infusion, fetal ACTH secretion was stimulated by fetal iv infusion of sodium nitroprusside (50 micrograms/min). In all groups, fetal plasma ACTH increased during the cortisol infusions, perhaps reflecting a circadian variation in fetal ACTH secretion which was not suppressed by cortisol. The endogenous increase in fetal ACTH during cortisol infusions produced apparently nonsteady state changes in fetal plasma cortisol concentrations. Cortisol infusion produced dose-related increases in the fetal plasma cortisol concentration. The highest rate of cortisol infusion increased fetal plasma cortisol to between 50 and 60 ng/ml. However, none of the cortisol infusions significantly suppressed fetal PRA or reduced the magnitude of the ACTH response to nitroprusside. The results demonstrate that acutely stimulated fetal ACTH secretion is not regulated by cortisol negative feedback in the last few days of fetal life. Reduction in negative feedback efficacy may allow the preparturient rise in cortisol secretion that is responsible for stimulating parturition in this species.

Effects on maternal and fetal steroid concentrations of induction of parturition in the sheep by inhibition of 3 beta-hydroxysteroid dehydrogenase.

Changes in circulating steroid hormones, the incidence of myometrial contractions, and the onset of labour were all monitored after administration of the 3 beta-hydroxysteroid dehydrogenase inhibitor, epostane, to chronically catheterized ewes and fetuses near term. In all animals the drug induced delivery 33-36 h after injection or infusion into the ewe with the birth of live healthy lambs which showed normal subsequent development. Epostane induced immediate, permanent falls in both maternal and fetal plasma progesterone concentrations, accompanied by increased PGF metabolite concentrations in the uterine vein beginning 15 min after treatment. Of the other hormonal changes observed, the most striking was the pronounced drop in both maternal and fetal plasma cortisol. In the fetus this fall was followed by increasing concentrations of circulating ACTH which eventually restored the cortisol levels. By 12-24 h after epostane a substantial overshoot had occurred and at 27-30 h the fetal plasma cortisol concentrations were as high as those seen during normal parturition at term. No significant changes in maternal plasma oestradiol-17 beta could be detected after epostane treatment or during labour. The incidence of slow myometrial contractions increased significantly during the second 3-h period after epostane, although their duration did not change. Contraction patterns typical of first stage labour were seen from 20 to 24 h. These results show that epostane may be used as a safe, predictable inducing agent in sheep if given 6-10 days before term; the lambs showed no signs of prematurity despite their lowered plasma cortisol concentrations which persisted for some hours before labour was induced.

Diurnal variations in plasma concentrations of cortisol, prolactin, growth hormone and glucose in the fetal sheep and pregnant ewe during late gestation.

We have measured fetal and maternal plasma concentrations of cortisol, prolactin, GH and glucose in samples collected during a 24-h period in 14 animals between 127 and 142 days of gestation. There was a significant increase in both the mean daily plasma cortisol concentration and mean daily coefficient of variation (C.V.) of plasma cortisol concentrations after 135 days of gestation. There was also a significant variation in the fetal plasma cortisol concentrations with a peak occurring at 19.00 h. There was a significant sinusoidal diurnal rhythm in the plasma prolactin concentrations in both the fetal sheep and pregnant ewe and the maximal prolactin concentrations occurred between 19.00 and 23.00 h (fetal) and 21.00 and 01.00 h (maternal). Although no significant diurnal variation was detected in fetal plasma GH concentrations, there was a significant sinusoidal diurnal rhythm in the plasma GH concentrations of the pregnant ewe and the maximal maternal GH concentrations occurred between 21.00 and 01.00 h. Both the fetal and maternal plasma glucose concentrations showed a significant sinusoidal diurnal rhythm. The maximal maternal and fetal glucose concentrations were measured between 21.00 and 01.00 h and between 23.00 and 03.00 h respectively. We have therefore established that diurnal variations in plasma cortisol and prolactin concentrations exist prenatally. Whether the presence of such hormonal rhythms reflects the activity of an endogenous fetal circadian pacemaker remains to be established.

Sensitivity of cortisol-induced inhibition of ACTH and renin in fetal sheep.

Previous experiments demonstrated that increases in ovine fetal plasma cortisol concentration to maximal stress levels suppressed fetal plasma renin activity and completely inhibited fetal adrenocorticotropin (ACTH) responses to subsequent stress. This study was designed to quantitate the suppressive action of cortisol on both ACTH and renin. Fetal sheep between 117 and 131 days gestation were surgically prepared with chronically implanted catheters. At least 4 days after surgery, vehicle or cortisol (0.25, 0.5, 1, 2, or 3 micrograms/min) were infused for 5 h. One hour after the end of the vehicle or cortisol infusion, fetal ACTH and renin secretion were stimulated by intravenous infusion of sodium nitroprusside. Cortisol infusions suppressed basal plasma renin activity (caused by suppression of plasma renin concentration) to degrees that were related to the increases in fetal plasma cortisol concentration. After cortisol infusions, renin responses to hypotension were apparently suppressed to degrees not obviously related to the rate of cortisol infusion. Fetal plasma ACTH responses to hypotension were completely suppressed by increases in total and unbound fetal plasma cortisol concentration 1.6 and 1.7 ng/ml, respectively. These results demonstrate a high sensitivity of the fetal hypothalamopituitary unit and renin-angiotensin system to cortisol.

Plasma growth hormone concentration in the chronically catheterized ovine fetus during spontaneous term delivery and premature delivery induced by continuous intravascular infusion of low doses of adrenocorticotropin or cortisol to the fetus

Fetal plasma growth hormone concentrations were measured in 15 pregnant ewes over the last 5 days before delivery. In five chronically catheterized pregnant ewes that underwent spontaneous vaginal delivery 146 ± 2 days (mean ± SD) of gestation, fetal plasma growth hormone concentrations fell from 124.6 ± 44.1 ng · ml−1 5 days before delivery to 35.2 ± 31.3 ng · ml−1 at delivery. In three fetuses in which premature delivery was induced by the infusion of cortisol to the fetus at 128 days of gestation, fetal plasma growth hormone levels fell from 195 ± 19.1 ng · ml−1 to 70.7 ± 25.5 ng · ml−1 over the last 5 days of intrauterine life. In seven fetuses in which premature delivery was induced with infusion of synthetic adrenocorticotropin to the fetus beginning at 120 or 130 days of gestation, the fetal plasma growth hormone level did not fall (175.6 ± 75.7 to 158.9 ± 60.1 ng · ml−1). Fetal plasma cortisol concentrations at delivery were significantly higher in the cortisol-infused fetuses (214 ± 38.4 ng · ml−1) than in both control (94.4 ± 33.7 ng · ml−1) and adrenocorticotropic hormone-infused fetuses (94.5 ± 31.9 ng · ml−1). The fall in the fetal plasma growth hormone level in cortisol-induced fetuses may be due to the higher fetal plasma cortisol concentrations achieved in the cortisol-infused compared with the adrenocorticotropic hormone-infused fetuses in which no comparable decrease in growth hormone was observed. These findings suggest that there are significant differences in the fetal response to various experimental regimens used for the induction of premature labor in the sheep.

Androstenedione metabolism in the late gestation sheep fetus.

We have determined metabolic parameters for androstenedione (A) in chronically catheterized late gestation (day 130) sheep fetuses. The MCR (MCRA) was 3210 +/- 229 (SEM, n = 12) ml/min, the fetal arterial whole blood concentration of A [A] was 65 +/- 5 pg/ml, and the blood production rate (PRA) was 204 +/- 20 ng/min. Pulsatile administration of ACTH in amounts that raised fetal arterial plasma cortisol concentrations by 5- to 7-fold increased [A] to 154 +/- 20 pg/ml and PRA to 471 +/- 31 ng/min with no change in MCRA. In the presence of metopirone to block fetal adrenal cortisol output, ACTH treatment still provoked elevations in [A] (to 198 +/- 23 pg/ml) and PRA (539 +/- 158 ng/min), without altering MCRA. The major radiolabeled product in blood of infused [3H]A was [3H]testosterone; smaller amounts of phenolic steroids were formed. Extensive metabolism of [3H]A occurred in whole blood in vitro. The major product was [3H]testosterone; the 17-oxidoreductase activity was associated with the red blood cells. Umbilical vein [A] was greater than umbilical artery [A]; ACTH treatment increased [A] in both vessels. Concomitant metopirone abolished the arteriovenous difference by eliminating the ACTH-induced increase in venous [A], although arterial [A] rose significantly. The venous [A] and the arteriovenous gradient were restored with exogenous glucocorticoid treatment to the fetus. Collagenase-dispersed fetal adrenal cells secreted A. Adrenal cells from fetuses pretreated with ACTH in vivo had higher basal and ACTH-induced output of A in vitro than cells from fetuses pretreated with saline in vivo. We conclude that the MCRA in fetal sheep is extremely high, in part due to conversion of A to testosterone in fetal blood. The elevated PRA after ACTH plus metopirone and the lack of an umbilical arteriovenous gradient of [A] in this, but not other groups of fetuses, suggests a source of A production independent of the cortisol-induced changes in the placenta. Direct evidence is provided for fetal adrenal secretion of A which is enhanced by ACTH pretreatment of the fetus in vivo and for the utilization of circulating A in the fetus as a precursor for estrogen in both fetal and maternal compartments.

Corticotropin-releasing factor-induced adrenocorticotropic hormone release in the sheep fetus: Blockade by cortisol

We administered intravenous injections of synthetic ovine corticotropin-releasing factor to chronically cannulated sheep fetuses and monitored fetal plasma adrenocorticotropic hormone and cortisol concentrations. The three doses of corticotropin-releasing factor used (10, 100, or 1000 ng · kg−1) increased fetal plasma adrenocorticotropic hormone; fetal plasma cortisol levels rose with the highest dose of corticotropin-releasing factor. Administration of corticotropin-releasing factor at these concentrations did not change fetal heart rate or blood pressure. Elevation of fetal plasma cortisol levels to 40 to 80 ng · ml−1 by infusions of the steroid blocked the adrenocorticotropic hormone responses to all three doses of corticotropin-releasing factor. These data indicate that corticotropin-releasing factor can increase plasma adrenocorticotropic hormone concentrations in the late-gestation fetus and that these increases can be blocked by elevations in fetal plasma cortisol levels within a physiologic range. This suggests that cortisol modulates adrenocorticotropic hormone release by the fetal pituitary gland late in gestation.

Physiological inhibition of ovine fetal plasma renin activity by cortisol.

The purpose of this study was to test the hypothesis that physiological increases in the fetal plasma cortisol concentration after basal and stimulated levels of PRA and vasopressin. Seven fetal sheep, between 121 and 131 days gestation, were infused with cortisol (4 micrograms/min) or vehicle for 5 h. One hour after the end of cortisol or vehicle infusion, sodium nitroprusside was infused into the fetus (100 micrograms/min, iv) to stimulate fetal hormone secretion. Cortisol, but not vehicle, infusion increased the fetal plasma cortisol concentration and decreased fetal PRA, but did not alter the fetal plasma vasopressin concentration. Cortisol-infused fetuses responded to nitroprusside with slightly smaller PRA responses but with equal vasopressin responses compared to those of vehicle-infused controls. Fetal blood pressure was not affected by either cortisol or vehicle infusion. Nitroprusside caused a slightly greater reduction in pressure in fetuses receiving cortisol infusion compared to those receiving the vehicle. We conclude that physiological increases in fetal plasma cortisol decrease fetal PRA without altering the fetal plasma vasopressin concentration. The results suggest that repeated fetal stress might produce progressive reduction of fetal PRA activity and might, therefore, alter cardiovascular homeostasis.

Activation of ovine fetal adrenal function by pulsatile or continuous administration of adrenocorticotropin-(1-24). I. Effects on fetal plasma corticosteroids.

ACTH given as a continuous infusion to fetal sheep causes an increase in plasma cortisol concentrations and premature labor. However, the effects on fetal adrenal responsiveness in vivo and the mode of ACTH administration on plasma corticosteroids are unknown. We examined the effects on plasma corticosteroids of giving the same total amount of ACTH to fetal sheep in utero either as pulses (P-ACTH; 66.7 ng/min for 15 min every 2 h) or continuously (C-ACTH; 0.5 micrograms/h) for 72 h. We determined the changes in vivo in fetal adrenal responsiveness during P-ACTH treatment, and we examined the ability of continued P-ACTH administration to induce premature labor. Both modes of ACTH administration led to a significant (P less than 0.05) increase in the fetal plasma cortisol (F) concentration compared with that in saline-treated controls, but C-ACTH resulted in significantly higher (P less than 0.05) F values than P-ACTH treatment. There was a small increase in the F-binding capacity of fetal plasma during both P-ACTH and C-ACTH, but there was no difference in the cortisol-binding capacity between the two treatments. Twenty minutes from the start of P-ACTH, there was an acute elevation in plasma F to values similar to those found with C-ACTH administration. The magnitude of this response rose significantly (P less than 0.05) between days 1-4 of P-ACTH treatment. There was no significant change in fetal plasma corticosterone during either P-ACTH or C-ACTH, resulting in a 4- to 6-fold increase in the plasma F to corticosterone ratio of both groups. In animals in which P-ACTH treatment was continued beyond 72 h, fetal plasma F continued to rise, and premature labor occurred after 99.0 +/- 4.1 (+/- SE) h. Fetal adrenal weights were not significantly different between P-ACTH for 72 or 100 h or C-ACTH for 72 h, although in each of these groups, the glands were heavier than those in control fetuses. We conclude that activation of fetal adrenal function is demonstrable in vivo during P-ACTH administration. This is reflected by selective F hypersecretion and may lead to premature delivery.

Negative feedback regulation of adrenocorticotropin secretion by cortisol in ovine fetuses.

The purpose of this study was to test the hypothesis that physiological increases in the fetal plasma cortisol concentration inhibit fetal ACTH responses to stress. Fetal sheep, between 121 and 131 days gestation, were infused with cortisol (4 micrograms/min) or vehicle for 5 h. One hour after the end of the cortisol or vehicle infusion, fetuses were infused with sodium nitroprusside (100 micrograms/min) to stimulate fetal ACTH and adrenal corticosteroid secretion. Cortisol, but not vehicle, elevated fetal plasma cortisol and suppressed the fetal ACTH and cortisol responses to nitroprusside. Cortisol and 11-deoxycortisol concentrations were significantly correlated in fetal plasma samples drawn during experiments in which cortisol was not infused; however, the cortisol to 11-deoxycortisol ratio was significantly increased during the infusion of nitroprusside. Fetal heart rate increased during vehicle infusion and decreased during cortisol infusion. Fetal blood pressure was not altered by either cortisol or vehicle infusion. Cortisol infusion increased fetal blood hemoglobin concentration, decreased maternal blood hemoglobin concentration, and produced metabolic acidosis in both mother and fetus. Vehicle infusion did not alter either fetal or maternal hemoglobin or pH. The data do not suggest an obvious mechanism for the cortisol-induced changes in fetal and maternal pH and hemoglobin or in fetal heart rate. However, some of the changes might be attributable to changes in fetal sympathetic outflow or to fluid shifts. We conclude that physiological increases in fetal plasma cortisol concentration: 1) inhibit subsequent ACTH responses to stress and 2) alter fetal cardiovascular function.

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.

Induction of parturition in sheep by low dose intrafetal infusion of synthetic adrenocorticotropin-(1-24) at 120-130 days gestation.

ACTH infusions into fetal sheep have been extensively used as a method of inducing premature parturition and the investigation of the associated endocrine and maturational changes in the fetus and ewe. Synthetic ACTH [ACTH-(1–24)] has been generally used in doses of 4–10 μg/h to induce parturition. These dose rates greatly exceed calculated endogenous fetal blood production rates for ACTH. The present study was designed to investigate the endocrine changes occurring in fetal and maternal ovine plasma during the induction of premature delivery with continuous infusion of a more physiological dose [1 μg ACTH-(1–24)/h]. The effect of ACTH-(1–24) infusions to the fetus at 120 or 130 days gestation were compared with appropriate gestational age controls. During ACTH-(1–24) infusion, the fetal plasma cortisol concentration in both age groups rose at similar rates. Furthermore, levels at delivery were equal to those observed in normal term fetuses. Where possible, three-parameter exponential curves were fitted t...

Fetal and adult hemoglobin in the chronically catheterized sheep fetus.

The switch from fetal to adult hemoglobin (Hb) has been investigated in fetal and newborn lambs. In the period between 125 and 145 days gestation, the proportion of fetal cells containing adult Hb increased significantly in catheterized fetuses. This increase paralleled the rise in fetal plasma cortisol under several different experimental conditions. However, infusion of synthetic adrenocorticotropin (ACTH1-24) into the fetus, which increased fetal plasma cortisol concentrations to levels slightly higher than observed at term, did not bring about any increase in the proportion of cells containing adult Hb. Increasing fetal plasma prolactin (PRL) concentration either by infusion of PRL or by stimulating endogenous PRL release with thyrotropin-releasing hormone (TRH) did not influence the time or rate of the switch. The fetal reticulocyte count was significantly higher in blood samples taken at the time of catheterization in fetuses of 103-115 days gestation than at 116-128 days gestation. In one repeatedly sampled fetus of adult type Hb AB, Hb C was observed at the time when the fetus was anemic. At birth the number of cells containing adult Hb was significantly higher in catheterized lambs than in nonoperated controls.

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.

Changing patterns of steroid production in the fetus and placenta and their effects on development.

A variety of radioimmunoassays specifically characterized for use with fetal and maternal ovine plasma have been used to measure steroid hormone concentrations in small plasma samples drawn simultaneously from mother and fetus. By repeated sampling from the same animal preparation the changes over time of plasma concentrations of cortisol, pregnenolone and its sulphate, and oestrone and oestrone sulphate have been systematically studied. In animals delivering spontaneously at term the fetal plasma cortisol concentration rises between 120 and 130 days gestation and plays an important part in the maturation of several vital physiological systems, including the fetal thyroid axis. In normal term deliveries and premature deliveries induced by synthetic adrenocorticotropin (ACTH(1-24), 1 microgram h-1), the concentration of oestrone sulphate in maternal plasma increases before the fetal plasma concentration. Fetal and maternal oestrogens are probably important in the control of the low-grade tonic myometrial activity that occurs throughout gestation, in the initiation of labour and in the control of uterine blood flow. Low-grade tonic myometrial activity affects fetal oxygenation, fetal breathing and the fetal sleep state and may constitute a pathway through which the mother influences fetal development, with important physiological and possibly pathological consequences.

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.