Neuroendocrine regulation of pituitary–adrenal function during fetal life

1996 ◽  
Vol 135 (2) ◽  
pp. 153-165 ◽  
Author(s):  
AN Brooks ◽  
DM Hagan ◽  
DC Howe
Keyword(s):  
Plasma Concentrations ◽  
Adrenal Function ◽  
Late Gestation ◽  
Neuroendocrine Regulation ◽  
Fetal Life ◽  
Acth Secretion ◽  
Feedback Effects ◽  
Fetal Plasma ◽  
Fetal Organ ◽  
Organ Systems

Brooks AN, Hagan DM, Howe DC. Neuroendocrine regulation of pituitary–adrenal function during fetal life. Eur J Endocrinol 1996;135:153–65. ISSN 0804–4643 During late gestation there is a rise in the concentration of corticosteroids in the fetal circulation that is essential for the coordinated maturation of many fetal organ systems and is a key component in the endocrine pathway leading to the onset of birth. Fetal plasma concentrations of adrenocorticotrophin (ACTH) increase during late, gestation and this rise precedes the increase in plasma corticosteroids. Paradoxically, ACTH and cortisol concentrations increase concomitantly even though cortisol would normally be expected to exert negative feedback effects to inhibit pituitary ACTH secretion. Elucidating the neuroendocrine signals that cause the increase in fetal ACTH, despite the elevated concentrations of cortisol at this time, will therefore provide vital clues as to the trigger for fetal organ maturation and birth. This article describes the normal ontogeny of the hypothalamo–pituitary–adrenal axis, discusses the neuroendocrine signals that trigger the increase in fetal ACTH secretion and provides potential explanations for the concomitant rise in ACTH and cortisol. AN Brooks, MRC Reproductive Biology Unit, 37 Chalmers Street, Edinburgh, EH3 9EW, Scotland, UK

scholarly journals Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus

2003 ◽  
Vol 176 (2) ◽  
pp. 175-184 ◽  
Author(s):  
S Gupta ◽  
N Alfaidy ◽  
AC Holloway ◽  
WL Whittle ◽  
SJ Lye ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Fetal Liver ◽  
Reductase Activity ◽  
Plasma Concentrations ◽  
Hydroxysteroid Dehydrogenase ◽  
Late Gestation ◽  
Concurrent Administration ◽  
Fetal Plasma ◽  
Fetal Organ

In the late-gestation sheep, increased fetal plasma cortisol concentration and placental oestradiol (E(2)) output contribute to fetal organ maturation, in addition to the onset of parturition. Both cortisol and E(2) are believed to regulate the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which interconverts bioactive 11-hydroxy glucocorticoids and their inactive 11-keto metabolites. 11beta-HSD1, abundantly expressed in fetal liver, operates primarily as a reductase enzyme to produce bioactive cortisol and thus regulates local hepatic glucocorticoid concentrations. Cortisol acts through the glucocorticoid receptor (GR) present in the liver. In this study, we examined the effects of cortisol and E(2) on hepatic 11beta-HSD1 and GR in the liver of chronically catheterized sheep fetuses treated with saline (n=5), cortisol (1.35 mg/h; n=5), saline+4-hydroxyandrostendione, a P450 aromatase inhibitor (4-OHA; 1.44 mg/h; n=5), or cortisol+4-OHA (n=5). Cortisol infusion resulted in increased plasma concentrations of fetal cortisol and E(2); concurrent administration of 4-OHA attenuated the increase in plasma E(2) concentrations. Using immunohistochemistry, we showed that fetal hepatocytes expressed both 11beta-HSD1 and GR proteins. Cortisol treatment increased GR in both cytosol and nuclei of hepatocytes; concurrent administration of 4-OHA was associated with distinct nuclear GR staining. Western blot revealed that cortisol, in the absence of increased E(2) concentrations, significantly increased concentrations of 11beta-HSD1 (34 kDa) and GR (95 kDa) proteins. 11beta-HSD1 enzyme activity was measured in the liver microsomal fraction in the presence of [(3)H]cortisone (10(-)(6) M) or [(3)H]cortisol (10(-)(6) M) and NADPH (reductase activity) or NADP(+) (dehydrogenase activity) respectively. 11beta-HSD1 reductase activity was significantly greater in the presence of cortisol. In summary, we found that, in sheep during late gestation, cortisol increased both 11beta-HSD1 and GR in the fetal liver, and these effects were accentuated in the absence of increased E(2).

Prostaglandin E2 enhances AVP-stimulated but not CRF-stimulated ACTH secretion from cultured fetal sheep pituitary cells

1992 ◽  
Vol 132 (1) ◽  
pp. 33-38 ◽  
Author(s):  
A. N. Brooks ◽  
F. Gibson
Keyword(s):  
Direct Action ◽  
Specific Interaction ◽  
Plasma Concentrations ◽  
Concomitant Administration ◽  
Late Gestation ◽  
Prostaglandin E ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Fetal Plasma

ABSTRACT This study examined the ability of prostaglandin E2 (PGE2) to regulate ACTH secretion from cultured anterior pituitary cells of fetal sheep between days 130 and 140 of gestation (term = 145 days). Corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) induced dose-dependent (0·1–1000 nmol/l) increases in ACTH secretion from fetal sheep pituitary cells maintained in culture for 6 days, with AVP being significantly (P<0·01) more potent than CRF. PGE2 (1000 nmol/l) significantly (P<0·05) enhanced the ability of AVP, but not CRF, to stimulate ACTH secretion. However, PGE2 given alone (0·1–1000 nmol/l) had no effect on ACTH secretion. Concomitant administration of CRF and AVP induced a greater release of ACTH than after treatment with either peptide alone, a synergistic interaction which was unaffected by simultaneous administration of PGE2. These results provide evidence for a direct action of PGE2 on ACTH secretion from the fetal sheep pituitary gland via a specific interaction with AVP. This interaction may allow increased fetal plasma concentrations of PGE2, seen during late gestation, to stimulate fetal pituitary–adrenal maturation. Journal of Endocrinology (1992) 132, 33–38

scholarly journals Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hepatic Glucose ◽  
Molar Percent ◽  
Glucose Output

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

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

The effects of cortisol on the growth rate of the sheep fetus during late gestation

1996 ◽  
Vol 151 (1) ◽  
pp. 97-105 ◽  
Author(s):  
A L Fowden ◽  
J Szemere ◽  
P Hughes ◽  
R S Gilmour ◽  
A J Forhead
Keyword(s):  
Growth Rate ◽  
Plasma Glucose ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
The Body ◽  
Late Gestation ◽  
Crown Rump Length ◽  
Fetal Plasma ◽  
Normal Term ◽  
Sheep Fetus

Abstract Using indwelling crown–rump length (CRL)-measuring devices, the growth rate of sheep fetuses was monitored during late gestation and after experimental manipulation of fetal plasma cortisol by exogenous infusion and fetal adrenalectomy. In intact control fetuses, the increment in CRL declined progressively during the last 20–25 days of gestation: mean ± s.e.m. values fell from 5·5 ± 0·4 mm/day (n=12) at 21–25 days before delivery to 2·5 ± 0·3 mm/day (n=12) in the last 5 days before birth (P<0·01). These changes closely parallelled the normal prepartum increase in fetal plasma cortisol which rose from 19·3 ±3·3 nmol/l (n=10) at 21–25 days before birth to 177·4 ± 19·0 nmol/l (n=10) in the final 5 days before delivery (P<0·01). When this cortisol surge was prevented by fetal adrenalectomy, there was no decrease in CRL increment towards normal term: mean CRL increment in the 5 days before normal term (4·8 ± 0·6 mm/day, n=5) was similar to that observed at 21–25 days before term (4·7 ± 0·4 mm/day, n=5). At delivery at term, the body weight (4·116 ± 0·280 kg, n=5) and CRL (51·9 ± 1·7 cm, n=5) of the adrenalectomized fetuses were significantly greater than the corresponding values in their sham-operated controls (2·877 ± 0·070 kg and 47·1 ±1·6 cm, n=6, respectively). In contrast with the sham-operated controls, plasma glucose and insulin levels in the adrenal-ectomized fetuses decreased towards term. Infusion of cortisol into the preterm fetus for 5 days increased fetal plasma cortisol to term levels and decreased the CRL increment to a value (1·8 ± 0·5 mm/day, n=8) which was similar to that observed in untreated controls during the last 5 days before spontaneous delivery at term (2·1 ± 0·3 mm/day, n=6). There were no significant alterations in the fetal arterial concentrations of plasma glucose or insulin in response to fetal cortisol infusion. When all the data were combined irrespective of treatment or proximity to delivery, the fetal plasma concentrations of cortisol (P<0·001) and glucose (P<0·04), but not insulin (P>0·05), had a significant effect on the fetal CRL increment measured over 5-day periods during the last 25–30 days of gestation. These findings show that cortisol inhibits growth of the axial skeleton in the sheep fetus during late gestation. They also indicate that the prepartum cortisol surge may be responsible for the normal decline in fetal growth rate observed towards term in this species. Journal of Endocrinology (1996) 151, 97–105

Corticotropin-releasing factor in the ovine fetus and pregnant ewe: role of placenta

1991 ◽  
Vol 261 (4) ◽  
pp. R995-R1002 ◽  
Author(s):  
M. Keller-Wood ◽  
C. E. Wood
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Late Pregnancy ◽  
Maternal Plasma ◽  
Corticotropin Releasing Factor ◽  
Late Gestation ◽  
Fetal Plasma ◽  
Ovine Fetus ◽  
Arterial Plasma ◽  
Pregnant Ewe

In the sheep, maternal plasma adrenocorticotropic hormone and cortisol are increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone rise precipitously in late gestation. To test whether the ovine placenta secretes corticotropin-releasing factor (CRF) into either the maternal or fetal circulation, pregnant ewes and their fetuses were prepared with femoral arterial catheters and uterine and umbilical venous catheters. Samples were taken from all sites before and during hypoxia. There was no difference in CRF concentration across the placenta in the mothers or the fetuses under resting or hypoxemic conditions, but maternal and fetal arterial plasma CRF concentrations increased between 128 and 145 days. In a second study, maternal and fetal femoral venous plasma CRF concentrations were measured 1-19 days before spontaneous parturition. The mean concentration increased 8.6 +/- 0.6 pg/ml 11-19 days before parturition to 13.0 +/- 1.0 and 13.2 +/- 1.4 pg/ml in fetuses 4-8 and 1-3 days before parturition, respectively. Maternal plasma concentrations did not significantly increase in the days closer to parturition. These studies demonstrate that there are low but measurable CRF concentrations in fetal and maternal sheep plasma but that these are not the result of tonic placental secretion of CRF.

scholarly journals Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels

2013 ◽  
Vol 305 (7) ◽  
pp. E868-E878 ◽  
Author(s):  
Nuermaimaiti Tuersunjiang ◽  
John F. Odhiambo ◽  
Nathan M. Long ◽  
Desiree R. Shasa ◽  
Peter W. Nathanielsz ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Maternal Diet ◽  
Control Diet ◽  
Plasma Concentrations ◽  
National Research Council ◽  
Late Gestation ◽  
Early Gestation ◽  
Fetal Organ ◽  
Insulin Dysregulation ◽  
Fetal Size

Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation ( day 75) or late ( day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater ( P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated ( P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics.

Kinetics of placental lactogen in mid- and late-gestation ovine fetuses

1992 ◽  
Vol 133 (1) ◽  
pp. 95-100 ◽  
Author(s):  
P. A. Schoknecht ◽  
W. B. Currie ◽  
A. W. Bell
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Exogenous Hormone ◽  
Entry Rate ◽  
Fetal Plasma ◽  
Kinetics Of

ABSTRACT Placental lactogen (PL) is found in fetal plasma throughout gestation, and PL receptors occur on many types of fetal cells. In this study, the entry rate of PL into the fetal circulation was estimated by injection of 125I-labelled ovine PL into two mid- and four late-gestation fetuses. At both ages, PL appears to be distributed into two body pools. One pool has a rapid half-life (approximately 9 min) and a volume of distribution approximately 8% of body weight, while the second pool has a longer half-life (approximately 45 min) and a distribution volume only 4% of body weight. The first pool is presumably blood plasma, but the physiological identity of the second pool is unknown. The effective half-life of PL is approximately 15 min, and the liver is suggested as a probable major site of degradation. These estimates were confirmed in late gestation by measuring fetal plasma concentrations of PL in response to a continuous infusion of unlabelled PL. The kinetic parameters estimated in this study can be used to determine the quantity of exogenous hormone required to alter PL concentration in fetal plasma in a predictable manner. Journal of Endocrinology (1992) 133, 95–100

Cortisol inhibits ACTH secretion in late-gestation fetal sheep

1991 ◽  
Vol 260 (2) ◽  
pp. R385-R388 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Negative Feedback ◽  
Plasma Cortisol ◽  
Sodium Succinate ◽  
Plasma Concentrations ◽  
Maternal Blood ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Acth Concentration ◽  
Negative Feedback Control

In sheep, parturition is initiated by an increase in fetal adrenal secretion of cortisol. In term fetuses, adrenocorticotropic hormone (ACTH) secretion is increased despite increasing plasma concentrations of cortisol. The present study was performed to investigate whether fetal ACTH secretion is under negative-feedback control by cortisol. Ten chronically catheterized fetal sheep (140 days gestation) were used in this study. Five were infused with hydrocortisone sodium succinate (10 micrograms/min) and five with 0.9% physiological saline for 5 h. Fetal and maternal blood samples were drawn at 1-h intervals. Infusion of hydrocortisone sodium succinate significantly increased fetal plasma cortisol concentration from 38.2 +/- 8.4 ng/ml to mean levels between 74.6 +/- 11.6 and 88.5 +/- 4.7 ng/ml. Fetal plasma ACTH concentration was significantly decreased from 129 +/- 36 to 31 +/- 5 pg/ml after 5 h of infusion. Infusion of saline did not alter fetal plasma cortisol or ACTH concentration. Neither of the infusions significantly altered maternal plasma concentrations of ACTH or cortisol, or fetal or maternal blood gases, or plasma concentrations of sodium or potassium. With one exception, all fetuses were born alive at 145 +/- 1 and 144 +/- 1 days gestation in the saline- and hydrocortisone sodium succinate-infused groups, respectively. The results of this study demonstrate that at 140 days gestation fetal ACTH secretion is under negative-feedback control by cortisol.

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