scholarly journals Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

2002 ◽  
Vol 173 (1) ◽  
pp. 143-150 ◽  
Author(s):  
AJ Forhead ◽  
AL Fowden
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Thyroid Hormones ◽  
Plasma Cortisol ◽  
Experimental Manipulation ◽  
Late Gestation ◽  
Converting Enzyme ◽  
Fetal Sheep ◽  
Near Term ◽  
Sheep Fetus

In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

scholarly journals Developmental Control of Iodothyronine Deiodinases by Cortisol in the Ovine Fetus and Placenta Near Term

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5988-5994 ◽  
Author(s):  
Alison J. Forhead ◽  
Katrina Curtis ◽  
Ellen Kaptein ◽  
Theo J. Visser ◽  
Abigail L. Fowden
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormones ◽  
Plasma Cortisol ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Perirenal Adipose Tissue ◽  
Deiodinase Activity ◽  
Serum T4 ◽  
Ovine Fetus ◽  
Near Term

Preterm infants have low serum T4 and T3 levels, which may partly explain the immaturity of their tissues. Deiodinase enzymes are important in determining the bioavailability of thyroid hormones: deiodinases D1 and D2 convert T4 to T3, whereas deiodinase D3 inactivates T3 and produces rT3 from T4. In human and ovine fetuses, plasma T3 rises near term in association with the prepartum cortisol surge. This study investigated the developmental effects of cortisol and T3 on tissue deiodinases and plasma thyroid hormones in fetal sheep during late gestation. Plasma cortisol and T3 concentrations in utero were manipulated by exogenous hormone infusion and fetal adrenalectomy. Between 130 and 144 d of gestation (term 145 ± 2 d), maturational increments in plasma cortisol and T3, and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and decrements in renal and placental D3 activities were abolished by fetal adrenalectomy. Between 125 and 130 d, iv cortisol infusion raised hepatic, renal, and perirenal adipose tissue D1 and reduced renal and placental D3 activities. Infusion with T3 alone increased hepatic D1 and decreased renal D3 activities. Therefore, in the sheep fetus, the prepartum cortisol surge induces tissue-specific changes in deiodinase activity that, by promoting production and suppressing clearance of T3, may be responsible for the rise in plasma T3 concentration near term. Some of the maturational effects of cortisol on deiodinase activity may be mediated by T3.

scholarly journals Plasma Leptin Concentration in Fetal Sheep during Late Gestation: Ontogeny and Effect of Glucocorticoids

Endocrinology ◽  
2002 ◽  
Vol 143 (4) ◽  
pp. 1166-1173 ◽  
Author(s):  
A. J. Forhead ◽  
L. Thomas ◽  
J. Crabtree ◽  
N. Hoggard ◽  
D. S. Gardner ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Gestational Age ◽  
Plasma Cortisol ◽  
In Utero ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Developmental Control ◽  
Near Term ◽  
Plasma Leptin ◽  
Sheep Fetus

Abstract The ontogeny and developmental control of plasma leptin concentration in the fetus are poorly understood. The present study investigated plasma leptin concentration in chronically catheterized sheep fetuses near term, and in neonatal and adult sheep. The effect of glucocorticoids on plasma leptin in utero was examined by fetal adrenalectomy and exogenous cortisol or dexamethasone infusion. In intact, untreated fetuses studied between 130 and 140 d (term, 145 ± 2 d), plasma leptin concentration increased in association with the prepartum cortisol surge. Positive relationships were observed between plasma leptin in utero and both gestational age and plasma cortisol. Plasma leptin was also inversely correlated with fetal paO2. The ontogenic rise in plasma leptin was abolished by fetal adrenalectomy. In intact fetuses at 123–127 d, plasma leptin was increased by infusions of cortisol (3–5 mg kg−1d−1, +127 ± 21%) for 5 d and dexamethasone (45–60 μg kg−1d−1, +268 ± 61%) for 2 d. However, the cortisol-induced rise in plasma leptin was transient; by the fifth day of infusion, plasma leptin was restored to within the baseline range. These findings show that, in the sheep fetus, an intact adrenal gland is required for the normal ontogenic rise in plasma leptin near term. Furthermore, fetal treatment with exogenous and endogenous glucocorticoids increases circulating leptin concentration in utero.

Developmental changes in plasma angiotensin-converting enzyme concentration in fetal and neonatal lambs

1998 ◽  
Vol 10 (5) ◽  
pp. 393 ◽  
Author(s):  
Alison J. Forhead ◽  
Robert Melvin ◽  
Vanessa Balouzet ◽  
Abigail L. Fowden
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Peak Plasma ◽  
Enzyme Concentration ◽  
Late Gestation ◽  
Developmental Changes ◽  
Converting Enzyme ◽  
Plasma Angiotensin ◽  
Near Term ◽  
Plasma Angiotensin Converting Enzyme

Relationships between plasma angiotensin-converting enzyme (ACE) and cortisol, and blood pressure were examined in chronically catheterized ewes and their fetuses during late gestation (111–141 days, term 145 2 days). Plasma ACE was also measured in non-pregnant adult ewes and in lambs over the first 5 weeks of life. In fetuses near term (136–141 days), plasma ACE was greater than in those studied earlier in gestation; overall, plasma ACE correlated with gestational age (r = 0.72). The ontogenic rise in plasma ACE was associated with prepartum increases in plasma cortisol (r = 0.67) and blood pressure (r = 0.66). No relationship was observed between plasma ACE and partial pressure of oxygen in utero. Peak plasma ACE concentration observed in fetuses near term was maintained in newborn lambs for 3 days after birth. By 2 weeks of postnatal age, plasma ACE had decreased to the value seen in non-pregnant adult ewes. Maternal plasma ACE was similar at all gestational ages studied, and was lower than that observed in non-pregnant ewes. Therefore, in the sheep fetus, plasma ACE increased towards term in association with the prepartum cortisol surge. Developmental changes in ACE activity may be partly responsible for the ontogenic rise in fetal blood pressure.

scholarly journals Ontogeny and Effects of Hypothalamic Pituitary Disconnection on Formation of Inositol Trisphosphate in Fetal Sheep Pituitary Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1440-1444 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Gestational Age ◽  
Plasma Cortisol ◽  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
The Impact ◽  
Pituitary Adrenal Axis ◽  
Sheep Fetus

In late gestation fetal sheep, the pituitary becomes increasingly responsive to stimulation by arginine vasopressin (AVP). This change appears to be one important factor mediating the plasma cortisol surge, a critical developmental event. It is not known precisely why pituitary corticotropes become more responsive at this time. In this study we examined the possibility that changes in second messenger generation [inositol trisphosphate (IP3)] are responsible. Two studies were undertaken. The first was an ontogeny study, where pituitaries were isolated from 100-, 120-, and 140-d gestational age (dGA) fetal sheep. Cells were cultured, stimulated with AVP, and the formation of IP3 assessed. The amount of IP3 generated increased with gestational age (percent increases from unstimulated controls were 4.6, 11.5, and 21.5 for 100, 120, and 140 dGA, respectively), with significant differences between the 140-dGA group and both earlier groups apparent. The second study examined the impact of 120-dGA hypothalamo-pituitary disconnection (HPD), which prevents corticotrope maturation, on responsiveness of pituitary cells isolated from 140-dGA fetuses. Cells were stimulated with AVP, and the formation of IP3 and secretion of ACTH were assessed. Significantly less IP3 was formed, and ACTH secreted in cells from HPD compared with control fetuses (IP3 and ACTH levels were 50% and 35% lower, respectively). Results from the HPD study demonstrate that the ontogenic changes in IP3 after AVP require an intact hypothalamic-pituitary-adrenal axis. These findings suggest that heightened second messenger generation may be a key reason for increased ACTH secretory responsiveness to AVP in the late gestation sheep fetus.

scholarly journals Role of thyroid hormones in the developmental control of tissue glycogen in fetal sheep near term

2009 ◽  
Vol 94 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Alison J. Forhead ◽  
Samantha Cutts ◽  
Phillippa A. Matthews ◽  
Abigail L. Fowden
Keyword(s):  
Thyroid Hormones ◽  
Fetal Sheep ◽  
Developmental Control ◽  
Near Term

Thyroid hormones and the mRNA of the GH receptor and IGFs in skeletal muscle of fetal sheep

2002 ◽  
Vol 282 (1) ◽  
pp. E80-E86 ◽  
Author(s):  
A. J. Forhead ◽  
J. Li ◽  
R. S. Gilmour ◽  
M. J. Dauncey ◽  
A. L. Fowden
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Thyroid Hormones ◽  
Gestational Age ◽  
Plasma Cortisol ◽  
Mrna Abundance ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Igf I ◽  
I Gene

Thyroid hormones are required for the normal development of skeletal muscle in utero, although their mechanism of action is poorly understood. The present study examined the effects of the thyroid hormones on the gene expression of the growth hormone receptor (GHR) and the insulin-like growth factors (IGFs) IGF-I and IGF-II, in skeletal muscle of fetal sheep during late gestation (term 145 ± 2 days) and after manipulation of plasma thyroid hormone concentration. Thyroidectomy at 105–110 days of gestation suppressed muscle GHR and IGF-I gene expression in fetuses studied at 127–130 and 142–145 days. Muscle GHR mRNA abundance remained unchanged with increasing gestational age in intact and thyroidectomized fetuses. In the intact fetuses, a decrease in muscle IGF-I gene expression was observed between 127–130 and 142–145 days, which coincided with the normal prepartum surges in plasma cortisol and triiodothyronine (T3). At 127–130 days, downregulation of muscle IGF-I mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2–3 mg · kg−1 · day−1 iv), which increased plasma cortisol and T3 concentrations to values seen near term. However, increasing plasma T3 alone by an infusion of T3 for 5 days (8–12 μg · kg−1 · day−1 iv) in intact fetuses at this age had no effect on GHR or IGF-I gene expression in skeletal muscle. In the thyroidectomized fetuses, no additional change in the low level of muscle IGF-I mRNA abundance was seen with increasing gestational age, but at 127–130 days, IGF-I gene expression was reduced further when plasma cortisol and T3 concentrations were increased by exogenous cortisol infusion. Muscle IGF-II mRNA abundance was not affected by thyroidectomy, gestational age, or exogenous hormone infusion. These findings show, in the sheep fetus, that thyroid hormones may influence the growth and development of skeletal muscle via changes in the local activity of the somatotrophic axis.

Cortisol feedback regulation of pulsatile ACTH secretion in fetal sheep during late gestation

1994 ◽  
Vol 267 (4) ◽  
pp. E521-E527 ◽  
Author(s):  
E. M. Apostolakis ◽  
L. D. Longo ◽  
S. M. Yellon
Keyword(s):  
Binding Capacity ◽  
Feedback Regulation ◽  
Late Gestation ◽  
Acth Secretion ◽  
Negative Feedback Regulation ◽  
Fetal Sheep ◽  
Secretory Rate ◽  
Ovine Fetus ◽  
Near Term

In fetal sheep, plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations increase during late gestation to surge within 72 h of birth (approximately 146 days gestation). To determine the feedback role of cortisol in control of pulsatile ACTH secretion, six chronically catheterized fetuses were treated with cortisol (1 microgram/h i.v.) for 96 h at 133 days gestation. Before (133 days), during (134 and 137 days), and after (142 days) cortisol treatment (5-min sampling for 2 h), ACTH pulses were evident in each fetus. At 134 days, ACTH pulse peak, nadir, and estimated secretory rate were significantly increased while frequency, amplitude, mean concentrations, and cortisol binding capacity (CBC) were unchanged. At 137 days, most characteristics of pulsatile ACTH secretion remained enhanced compared with pretreatment controls. At 142 days (96 h postinfusion), ACTH secretion parameters returned to pretreatment levels, but cortisol concentrations remained elevated. Cortisol infusion was then reinitiated at 142 days and, 22–24 h later, parameters of ACTH secretion increased except for amplitude, secretory rate, and CBC activity. The data indicate an absence of cortisol negative feedback regulation of pulsatile ACTH secretion. Rather, the ACTH rise that accompanied cortisol infusion suggests that cortisol exerts a positive feedforward influence on ACTH secretion in the ovine fetus near term.

Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme concentration in fetal sheep during late gestation

2003 ◽  
Vol 189 (5) ◽  
pp. 1467-1471 ◽  
Author(s):  
Heiner Zimmermann ◽  
David S Gardner ◽  
Juanita K Jellyman ◽  
Abigail L Fowden ◽  
Dino A Giussani ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzyme Concentration ◽  
Late Gestation ◽  
Converting Enzyme ◽  
Fetal Sheep

scholarly journals Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin

2009 ◽  
Vol 296 (2) ◽  
pp. E300-E304 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Signal Transduction ◽  
Arginine Vasopressin ◽  
Plasma Cortisol ◽  
Pituitary Cell ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Inositol 1,4,5 Trisphosphate ◽  
Sheep Fetus

Corticotrophs in the fetal sheep become increasingly responsive to arginine vasopressin (AVP) in late gestation. We previously reported that this may be due in part to corresponding increases in signal transduction (inositol 1,4,5-trisphosphate, IP3). These ontogenic changes are prevented by hypothalamo-pituitary disconnection (HPD), which also prevents fetal plasma cortisol concentrations from increasing in late gestation. This led us to hypothesize that cortisol is involved in mediating the changes in pituitary responsiveness. HPD was performed on fetal sheep at 120 days gestational age (dGA). Half of the HPD fetuses were infused with cortisol for 3 days beginning at 135–137 dGA (HPD+C). The remaining HPD fetuses and a group of sham-operated control fetuses were infused with saline. Pituitary cells were isolated and cultured. After 48 h, a subset of cells was stimulated with 100 nM AVP for 2 h, and the medium was collected for ACTH analysis. Another subset of cells was stimulated with 100 nM AVP for 30 min, and the formation of IP3 was determined. Plasma cortisol concentrations increased rapidly within the first 6 h after infusion (5.2 ± 1.9 to 29.7 ± 4.9 ng/ml) but did not increase thereafter. Cells from HPD+C and sham-operated fetuses secreted significantly more ACTH than those from HPD fetuses (% increase from control: 33.0 ± 8.8%, 47.9 ± 10.6%, and 11.9 ± 2.4%, respectively). IP3 formation was significantly increased in cells from HPD+C and sham-operated compared with HPD fetuses (% increase from control: 17.7 ± 4.4%, 18.9 ± 4.3%, and 4.6 ± 1.5%, respectively). These findings support the idea that cortisol plays a role in mediating the increase in pituitary responsiveness to AVP in the late-gestation fetal sheep.

Sign in / Sign up

Export Citation Format

Share Document