Prepartum adrenocortical maturation in the fetal foal: responses to ACTH1–24

1994 ◽  
Vol 142 (3) ◽  
pp. 417-425 ◽  
Author(s):  
M Silver ◽  
A L Fowden
Keyword(s):  
Amniotic Fluid ◽  
Plasma Cortisol ◽  
Critical Period ◽  
Maternal Plasma ◽  
Significant Rise ◽  
Late Gestation ◽  
Plasma Acth ◽  
Fetal Plasma ◽  
Period 2 ◽  
Time To Delivery

Abstract The present study was carried out on 19 chronically catheterized mares and fetuses in late gestation (term >320 days). In six animals which were monitored up to the time of delivery of a live foal, plasma and amniotic fluid cortisol concentrations remained low until 4–5 days before parturition when there was a rapid, significant rise (P<0·05) which was not accompanied by any corresponding changes in maternal plasma cortisol. Circulating fetal ACTH concentrations became more variable close to delivery and ANOVA revealed no significant increases during this critical period, although a negative correlation between plasma ACTH and time to delivery was observed (P<0·05). Tests on fetal adrenal responsiveness to exogenous ACTH1–24 were carried out on ten animals. Before 295 days of gestation no significant increases in fetal plasma cortisol above its basal level of 20–30 nmol/l could be elicited by ACTH, administered as a single i.v. injection (1–2 μg/kg). By 304 ± 3 days (mean ± s.e.m.) small but significant (P<0·05) increments in plasma cortisol were detected after ACTH, while in the oldest group (313 ±2 days) significant (P<0·01) 50–60% increments were seen throughout the test period (2 h). Only one fetus was tested within 3 days of delivery and here a fourfold rise in plasma cortisol was evoked by ACTH. When changes in endogenous levels of circulating ACTH and cortisol were monitored every 15 min over 1·5- to 2-h periods in late gestation, rises in ACTH were only accompanied by concomitant increases in plasma cortisol in fetuses within 5 days of delivery (correlation coefficient r=0·58, P<0·01). Before this time, plasma cortisol concentrations remained at basal levels irrespective of any fluctuations in plasma ACTH. These findings indicate that the adrenal cortex of the fetal foal is relatively quiescent and insensitive to ACTH for most of the latter part of gestation, but that a short rapid escalation in circulating cortisol precedes its delivery. Journal of Endocrinology (1994) 142, 417–425

Does the ovine placenta secrete ACTH under normoxic or hypoxic conditions?

1991 ◽  
Vol 260 (2) ◽  
pp. R389-R395 ◽  
Author(s):  
M. Keller-Wood ◽  
C. E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Late Pregnancy ◽  
Maternal Plasma ◽  
Late Gestation ◽  
Fetal Circulation ◽  
Fetal Plasma ◽  
Hypoxic Conditions ◽  
Ovine Placenta ◽  
Arterial Po2

In the sheep, maternal plasma cortisol is increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone (ACTH) rise precipitously in late gestation. In many species, the placenta contains ACTH. These experiments were designed to test whether the ovine placenta contains ACTH and whether there is net secretion of ACTH by the uteroplacental unit into either the maternal or fetal circulation. Pregnant ewes and their fetuses were prepared with maternal and fetal arterial and uterine and umbilical venous catheters. Arterial and venous samples were taken from both sides of the placenta before and during hypoxia induced by the ewe breathing 9-11% O2, and arteriovenous (a-v) differences in ACTH, PO2, PCO2, and progesterone were analyzed. A positive a-v difference in PO2 (48.2 +/- 3.4 mmHg) and negative a-v differences in PCO2 and progesterone (-3.5 +/- 0.7 mmHg and -25 +/- 5 ng/ml, respectively) were found across the placenta in the ewe, and a positive a-v difference in PCO2 (4.8 +/- 0.9 mmHg) and negative a-v differences in PO2 and progesterone (-8.1 +/- 1.5 mmHg and -13 +/- 3 ng/ml, respectively) were found across the placenta in the fetus, indicating that the umbilical and uterine venous catheters were properly placed. Hypoxia decreased fetal and maternal arterial PO2 from 22.8 +/- 1.3 to 13.8 +/- 0.7 and from 98.8 +/- 3.3 to 37.0 +/- 2.6 mmHg, respectively, and increased fetal and maternal arterial ACTH immunoreactivity from 95 +/- 60 to 2,676 +/- 795 and from 149 +/- 21 to 275 +/- 88 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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

1988 ◽  
Vol 255 (3) ◽  
pp. R412-R417 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Maternal Plasma ◽  
Renin Secretion ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Adrenal 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.

Short-term fluctuations in the concentration of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids from sheep during late pregnancy

1981 ◽  
Vol 59 (3) ◽  
pp. 261-267 ◽  
Author(s):  
J. R. G. Challis ◽  
J. E. Patrick ◽  
Jill Cross ◽  
J. Workewych ◽  
E. Manchester ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Allantoic Fluid ◽  
Late Pregnancy ◽  
Maternal Plasma ◽  
Significant Rise ◽  
Short Term ◽  
Fetal Plasma ◽  
Two Fluids ◽  
Paired Samples ◽  
Steroid Profiles

Fluctuations in the concentrations of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids were measured in samples taken at 10-min intervals over a 90-min period from three groups of sheep sampled at different times during late pregnancy. During the last 30 days of gestation there was a significant rise in the mean concentration of cortisol in fetal plasma and amniotic fluid and a significant correlation between the cortisol concentration in these two fluids. The concentration of cortisol in allantoic fluid exceeded that in amniotic fluid. The concentration of cortisol in fetal plasma varied in a pulsatile manner; however the coefficient of variation (CV) within animals was greater (36%) on days −11 to −20, relative to the day of parturition (day 0), than on days −21 to −30 or days −5 to 0 (15–19%). The CV values for cortisol in amniotic fluid and maternal plasma during the last 30 days of pregnancy were 20–50% and two to five times greater than the intraassay CV. The concentration of progesterone in amniotic fluid increased after day −20 but was not correlated with that in maternal plasma or fetal plasma. The concentrations of progesterone in paired samples of amniotic fluid and allantoic fluid were similar. The CV values for progesterone (18–34%) were similar in fetal and maternal plasma and amniotic fluid and did not change significantly during late pregnancy. Changes in the concentration of progesterone were unrelated to changes in cortisol. Interpretation of steroid profiles in fetal plasma and fluids through late pregnancy should take into account these short-term fluctuations in hormone concentrations.

Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep

1995 ◽  
Vol 73 (11) ◽  
pp. 1568-1573 ◽  
Author(s):  
Treena M. Jeffray ◽  
Edward T. M. Berdusco ◽  
John R. G. Challis ◽  
Megan Wallace ◽  
Abigail Fowden
Keyword(s):  
Plasma Cortisol ◽  
Binding Capacity ◽  
Strong Support ◽  
Significant Rise ◽  
Late Gestation ◽  
Total Plasma ◽  
Individual Values ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Corticosteroid Binding Globulin

The effects of incremental cortisol infusion or fetal adrenalectomy on plasma corticosteroid-binding capacity (CBC) were examined in sheep fetuses during late gestation (term ≈ 150 days). Cortisol, infused from day 120 at 1.5 mg/day for the first 3 days, 2.5 mg/day for the next 5 days, and 3.5 mg/day for the final 2 days, stimulated a significant rise in plasma CBC and immunoreactive corticosteroid binding globulin (CBG). There was a significant positive correlation between individual values for total plasma cortisol concentrations and CBC values. In contrast, fetal adrenalectomy at day 115 prevented the rise in plasma CBC found in intact fetuses at term. These experiments show that exogenous cortisol, given in a manner that mimics the prepartum rise in fetal plasma cortisol, stimulates CBG biosynthesis, whereas abolition of the cortisol rise prevents the increase in CBG. The study provides strong support for the proposal that the prepartum increase in CBG biosynthesis in fetal sheep occurs in response to the progressive rise in adrenal cortisol output by the fetus towards term.Key words: corticosteroid binding globulin, cortisol, adrenalectomy, fetus, sheep.

Premature birth of live lambs induced by pulsatile infusion of ACTH

1990 ◽  
Vol 124 (1) ◽  
pp. 99-107 ◽  
Author(s):  
R. J. MacIsaac ◽  
R. S. Carson ◽  
A. P. Horvath ◽  
E. M. Wintour
Keyword(s):  
Plasma Concentrations ◽  
Maternal Plasma ◽  
Sampling Time ◽  
Plasma Acth ◽  
Fetal Plasma ◽  
A Value ◽  
Normal Term ◽  
Acth Treatment ◽  
Normal Gestation ◽  
Pulsatile Infusion

ABSTRACT This study was designed to investigate the effects of pulsatile infusion of ACTH into ovine fetuses on the endocrine changes that precede parturition, the timing of birth and the subsequent survival of the lamb. Where appropriate, these parameters were compared with fetuses infused with pulses of saline and uninfused normal term fetuses. Ten fetuses received a 15-min infusion of synthetic ACTH(1–24) (79 ng/min) from day 125 (n=9) or day 126 (n=1) of gestation. Seven fetuses were born prematurely within 174±14 h (mean ± s.e.m.) after the commencement of the infusion, i.e. at 132 ± 0·6 days, whilst three died in utero at 130–131 days. When born all lambs could breath, walk and suckle. Of the seven premature lambs, four died 2–10 days after parturition but three survived for at least 12 months after birth. Fetuses infused with pulses of ACTH exhibited intermittent but very large increases in plasma ACTH values, with the first pulse, on day 1, increasing ACTH values from 5·1 ± 1·1 to 140 ± 31·3 pmol/l (P<0·001). At the next sampling time, ACTH values were not significantly different from preinfusion values. A similar plasma ACTH profile was observed on each subsequent day of ACTH treatment. In contrast, fetuses (n=4) infused with pulses of saline between 125 and 131 days exhibited fetal plasma concentrations of ACTH which ranged between 2 and 12 pmol/l for the majority of the time. Of the uninfused fetuses (n=8) that were studied during the last week of normal gestation, seven were born alive at 148·9± 1·0 days of gestation, whilst one lamb was stillborn at 146 days. In these fetuses, plasma concentrations of ACTH increased slowly to 35·6 ±2·4 pmol/l on the day before delivery with a further increase to 76·4± 3·9 pmol/l occurring on the day of delivery. In fetuses infused with pulses of ACTH there was also a significant (P< 0·001) increase in the fetal cortisol to corticosterone ratio from a value of 2·9 before the commencement of the infusion to 69·1 just before birth. In ewes bearing uninfused fetuses born at normal term, maternal plasma concentrations of progesterone on day 4 before delivery were significantly (P<0·05) lower than on day 5 before delivery. In comparison, in ewes bearing fetuses infused with pulses of ACTH, a significant (P<0·05) decrease from maternal plasma concentrations of progesterone on day 5 before delivery did not occur until day 1 before delivery. In ewes bearing uninfused or prematurely delivered fetuses infused with pulses of ACTH, maternal plasma concentrations of oestrogen did not significantly (P<0·01) increase until the day of parturition. It is concluded that a minimum of 6–7 days of ACTH treatment is required by the fetal adrenal for the induction of cortisol synthesis sufficient to produce the birth of viable lambs. However, premature lambs have a 57% mortality rate in the 2- to 10-day period after birth. Journal of Endocrinology (1990) 124, 99–107

Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation

1997 ◽  
Vol 152 (3) ◽  
pp. 379-386 ◽  
Author(s):  
M B Nicol ◽  
J J Hirst ◽  
D Walker ◽  
G D Thorburn
Keyword(s):  
Plasma Concentrations ◽  
Maternal Plasma ◽  
Late Gestation ◽  
Emg Activity ◽  
Fetal Sheep ◽  
Plasma Progesterone ◽  
Fetal Plasma ◽  
Progesterone Synthesis ◽  
Progesterone Metabolites ◽  
Vascular Catheters

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130–133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 ± 121%, n=5, P<0·05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74·4–81·1% and 58–65% respectively, P<0·05, n=5). Four ewes received Trilostane (25 mg i.v.), a 3β-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19·8 ± 8·0% and 39·5 ± 24·3% respectively, P<0·05). The incidence of fetal EOG activity increased from a pretreatment level of 26·8 ± 1·5 min/h to 30·3 ± 2·8 min/h at 1–6 h and to 35·0 ± 1·7 min/h (P<0·05) during the 7–12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1–6 h and 7–12 h after Trilostane treatment (19·5 ± 3·0 and 23·6 ± 5·5 min/h respectively, P<0·05) compared with pretreatment levels (11·2 ± 1·2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM. Journal of Endocrinology (1997) 152, 379–386

Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol administration to late-gestation ovine fetus

1998 ◽  
Vol 274 (3) ◽  
pp. E417-E425 ◽  
Author(s):  
T. M. Jeffray ◽  
S. G. Matthews ◽  
G. L. Hammond ◽  
J. R. G. Challis
Keyword(s):  
Plasma Cortisol ◽  
Late Gestation ◽  
Pars Intermedia ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Negative Feedback Regulation ◽  
Fetal Sheep ◽  
Pomc Mrna ◽  
Free Cortisol ◽  
Ovine Fetus

Plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH) rise in the late-gestation sheep fetus at approximately the same time as there is an increase in the plasma levels of corticosteroid- binding globulin (CBG). We hypothesized that intrafetal cortisol infusion during late pregnancy would stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and diminish glucocorticoid negative-feedback regulation of the fetal pituitary, leading to an increase in plasma ACTH concentrations. Cortisol was infused into chronically catheterized fetal sheep beginning at 126.1 ± 0.5 days of gestation and continued for 96 h. Control fetuses were infused with saline. In cortisol-infused fetuses, the plasma cortisol concentrations rose significantly from control levels (4.4 ± 0.6 ng/ml) to 19.3 ± 3.1 ng/ml within 24 h and remained significantly elevated throughout the infusion period. Plasma immunoreactive (ir) ACTH concentrations were significantly elevated in cortisol-infused fetuses within 24–48 h and remained significantly higher than in controls throughout the 96-h experimental period. Plasma free cortisol concentrations increased 10-fold and remained significantly elevated in cortisol-infused animals, despite a rise in plasma corticosteroid-binding capacity. Levels of pituitary proopiomelanocortin (POMC) mRNA in the fetal pars distalis and pars intermedia were 96 and 38% lower, respectively, after 96 h of cortisol infusion. Therefore physiological elevations of plasma cortisol, in the late-gestation ovine fetus, lead to increases in mean plasma irACTH concentrations, but this is not associated with increases in fetal pituitary POMC mRNA levels.

Determination of insulin-like growth factor-2 in feto-maternal circulation during human pregnancy

1992 ◽  
Vol 127 (4) ◽  
pp. 359-365 ◽  
Author(s):  
Toshiro Kubota ◽  
Shusaku Kamada ◽  
Makoto Taguchi ◽  
Takeshi Aso
Keyword(s):  
Amniotic Fluid ◽  
Umbilical Vein ◽  
Maternal Plasma ◽  
Cross Reactivity ◽  
Main Peak ◽  
Gel Chromatography ◽  
High Concentration ◽  
Maternal Circulation ◽  
Human Pregnancy ◽  
Fetal Plasma

In order to clarify the roles of insulin-like growth factors (IGFs) on the human maternal-fetal environment, IGF-2 and IGF-1 levels were investigated in human plasma and amniotic fluid during pregnancy. Initially, new radio-immunoassay (RIA) systems for human IGF-2 could be developed. The sensitivity of this assay was 17.5 pg/tube and the cross-reactivity with IGF-1 was 0.64%. The pattern of change of maternal plasma IGF-2 in early pregnancy differed from that of IGF-1, but both IGF levels increased progressively in the second half of gestation, and decreased to non-pregnancy levels in the puerperium. Maternal levels of IGF-2 were approximately seven times greater than those of IGF-1. The ratio of IGF-2 to IGF-1 was 3.2 in amniotic fluid. The IGF concentrations in amniotic fluid obtained in the second trimester were significantly greater than those of term specimens, and closely related to those of prolactin (PRL) in amniotic fluid. The highest IGF-2 to IGF-1 ratio (1 5.9) was found in umbilical vein plasma. On Sephadex G-150 gel-chromatography of maternal and fetal plasma at term, two apparent peaks of unsaturated IGF-2 binding protein (BP) could be detected in both 150 and 40 kilo dalton (kD) regions. One main peak of unsaturated IGF-2 BP could be determined in the 40 kD region in the amniotic fluid at term. High concentration of IGF-2 could be detected in feto-maternal circulation during human pregnancy. Moreover, it is strongly suggested that the releasing systems of IGFs in amniotic fluid are different from those in maternal or umbilical circulation.

Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens

1985 ◽  
Vol 63 (5) ◽  
pp. 500-508 ◽  
Author(s):  
G. Jenkin ◽  
G. Jorgensen ◽  
G. D. Thorburn ◽  
J. E. Buster ◽  
P. W. Nathaniels
Keyword(s):  
Plasma Cortisol ◽  
Intramuscular Injection ◽  
Maternal Plasma ◽  
Premature Delivery ◽  
Concomitant Treatment ◽  
Normal Delivery ◽  
Plasma Progesterone ◽  
Fetal Plasma ◽  
Single Intramuscular Injection ◽  
Maternal Administration

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 ± 7.7 h (mean ± SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20α-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11–13 days). Maternal plasma progesterone and 20α-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20α-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.

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