Biomedical subjects

T M Jeffray

Publications and source records attributed to T M Jeffray.

5 recordsLinked to original sources

PubMed1999

Effect of prenatal betamethasone administration on maternal and fetal corticosteroid-binding globulin concentrations.

OBJECTIVE: This study was undertaken to examine the effects of prenatal betamethasone administration on corticosteroid-binding globulin concentrations in maternal and fetal plasma and amniotic fluid. STUDY DESIGN: Two groups of patients with preterm labor at 24 to 35 weeks' gestation who were receiving prenatal betamethasone (2 intramuscular doses of 12 mg) were studied. Maternal plasma was obtained before and at variable intervals until 1 week after betamethasone administration. Umbilical cord blood and amniotic fluid samples were collected at the time of delivery. Samples were also collected from patients at risk for preterm delivery who did not receive glucocorticoids. RESULTS: Betamethasone suppressed maternal cortisol concentration by >70% within 24 hours of injection but did not significantly alter corticosteroid-binding capacity or relative concentrations of corticosteroid-binding globulin isoforms in either maternal or umbilical cord plasma. Betamethasone reduced corticosteroid-binding capacity in amniotic fluid within 24 hours of injection, and values remained suppressed 1 week after treatment. CONCLUSION: Maternal and fetal plasma corticosteroid-binding globulin concentrations were unchanged after maternal betamethasone administration at 24 to 32 weeks' gestation but amniotic fluid corticosteroid-binding globulin concentrations decreased significantly, suggesting different sites of either corticosteroid-binding globulin production or regulation or both.

Amniotic Fluid↗

PubMed1998

Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol administration to late-gestation 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 (i.r.) 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.

Adrenocorticotropic Hormone↗

PubMed1997

The effects of estradiol-17 beta infusion into fetal sheep in late gestation.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis of fetal sheep during late gestation is associated with increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and ultimately results in parturition. However, the mechanisms contributing to the concurrent increases in ACTH and cortisol are unclear. Plasma estradiol-17 beta (E2) concentrations increase progressively in the prepartum ovine fetus, and we hypothesized that E2 may influence HPA activity by affecting either basal and/or hypoxemia-stimulated ACTH release. We examined potential mechanisms, including altered expression of pro-opiomelanocortin (POMC) in fetal pituitary corticotrophs, and changes in corticosteroid binding globulin (CBG) and/or the enzymes 11 beta hydroxy steroid dehydrogenase (11 beta HSD)-1 or 11 beta HSD-2 in liver and placenta, that could alter negative feedback control. We infused fetal sheep at 127 d of gestation with either E2 (100 micrograms/24 h) or saline for 100 h. Fetal arterial blood samples were collected at 8 h intervals during the infusion of E2 or saline (n = 4), for measurement of basal plasma ACTH and cortisol concentrations, as well as plasma corticosteroid binding capacity (CBC). Placenta and fetal liver samples were collected at 100 h for measurement of placental 11 beta HSD-1 and 11 beta HSD-2 mRNA and hepatic CBG and 11 beta HSD-1 mRNA, by Northern blotting. Fetal pituitary samples were collected for measurement of POMC mRNA by in situ hybridization. In a separate experiment, fetuses were exposed to 2 h of hypoxemia at 75 h of E2 or saline infusion (n = 4), and fetal arterial blood samples were collected during the period of hypoxemia for measurement of plasma ACTH and cortisol concentrations. E2 infusion had no effect on basal plasma concentrations of ACTH or total cortisol, or on the stimulated levels of ACTH or total cortisol achieved in response to hypoxemia. Basal fetal pituitary POMC mRNA also did not change significantly with E2 infusion. No significant increases were observed in plasma CBC during E2 administration. However, hepatic CBG and 11 beta HSD-1 mRNA were significantly elevated in the livers of E2-treated fetuses. Placental 11 beta HSD-1 mRNA; but not 11 beta HSD-2 mRNA was increased by E2 treatment. These data do not support a direct effect of exogenous E2 at the level of basal or hypoxemia-stimulated ACTH output, but suggest that elevated E2 concentrations may alter the expression of genes encoding proteins implicated in tonic regulation of fetal HPA function.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1995

Corticosteroid-binding globulin (CBG) in fetal development.

In fetal sheep the prepartum increase in plasma cortisol concentration is associated with an increase in high affinity corticosteroid binding activity in plasma. This appears to reflect an increase in corticosteroid-binding globulin (CBG) biosynthesis from the fetal liver, and evidence is presented that hepatic CBG gene expression is increased by exposure to glucocorticoids in the fetus. Immunoreactive CBG is found in other fetal tissues, and CBG mRNA is present in fetal pituitary. CBG reduces the ability of cortisol to exert negative feedback on basal or CRH-stimulated ACTH output by fetal sheep pituitary cells in culture. We suggest that CBG interacts with cortisol in a manner that maintains a low negative feedback on the pituitary, and perhaps hypothalamus. This constitutes a component of the cascade of events that is associated with hypothalamic-pituitary-adrenal activation in the late gestation fetus, and with the onset of parturition.

Animals↗

PubMed1995

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

The effects of incremental cortisol infusion or fetal adrenalectomy on plasma corticosteroid-binding capacity (CBC) were examined in sheep fetuses during late gestation (term approximately 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.

Adrenal Cortex Hormones↗