Adrenocorticotrophin and Corticosteroid Changes During Dexamethasone Infusion to Intact and Synacthen Infusion to Hypophysectomized Foetuses

Abstract

Synacthen has been infused at 10 \g=m\g/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70 % and the plasma cortisol concentration by about 60 %.During the induction of premature parturition in sheep by the infusion of Synacthen into the foetus plasma adrenocorticotrophin (ACTH) concentra¬ tions first showed a small increase then this was followed by large fluctuations (Johnson et al. 1975). These results suggested that during Synacthen infusion ® Present address:

Induction of Premature Parturition in Sheep: Adrenocorticotrophin and Corticosteroid Changes During Infusion of Synacthen Into the Foetus

“…This is based on the observation that column chromatography of these samples show predominantly low molecular weight peptides ann on the fall in ACTH concentration to low values on stopping the infusion. The half-life for Synacthen calculated from the concentration achieved after infusion for 24 h is similar to that reported for ACTH in the foetal circula¬ tion ) and for Synacthen in hypophysectomized foetal sheep (Jones et al 1978) although it is shorter than that calculated from the decay curve. This discrepancy may be due to the slow release of Synacthen from tissue binding sites after stopping the infusion.…”

“…Also large fluc¬ tuations in the concentrations of ACTH follow closely those in the concen¬ tration of plasma corticosteroid, indicating that after the initial 24 h induction period the foetal adrenal is sensitive to ACTH (Liggins et al 1973;Bassett 8c Thorburn 1973;Madill 8c Bassett 1973). The observations of Liggins et al (1977) show that dexamethasone infusion into foetal sheep increases the foetal adrenal sensitivity to ACTH despite depressing ACTH secretion (Jones et al 1978). This indicates that as yet undefined maturational changes are occurring in the foetal pituitary-adrenal system that are not simply explained by changes in ACTH secretion.…”

Adrenal Cortex of Fetal Lamb: Changes After Hypophysectomy and Effects of Synacthen on Cytoarchitecture and Secretory Activity

“…At this stage some mature cells, with abundant smooth endoplasmic In contrast to the intact sheep fetus near term, the hypophysectomized animal has low plasma concentrations of cortisol (Barnes, Comline & Silver, 1977) and, without the prepartum cortisol surge, labour is not initiated and pregnancy is prolonged (Liggins, Kennedy & Holm, 1967). Infusion of exogenous ACTH will, however, induce parturition in such animals (Kendall, Challis, Jones, Ritchie & Thorburn, 1975;Jones, Kendall, Ritchie, Robinson & Thorburn, 1978). In the experiment described here, the effects of fetal hypophysectomy on the cell population of the adrenal cortex has been examined with light and electron microscopy.…”

Thromboxane B-2 in the plasma and amniotic fluid of late pregnant and periparturient sheep

“…The day of marking by an intact raddled ram was taken as Day 0 of pregnancy. Fetal, amniotic and maternal catheters were implanted at laparotomy between Days 100 and 125 of gestation by strictly aseptic procedures that have been described previously Jones, Kendall, Ritchie, Robinson & Thorburn, 1978). In 3 animals the fetus was hypophysectomized; the success of the procedure was confirmed by examination of the pituitary fossa and measurements of growth hormone and prolactin in fetal plasma (Jones et al, 1978).…”

“…Fetal, amniotic and maternal catheters were implanted at laparotomy between Days 100 and 125 of gestation by strictly aseptic procedures that have been described previously Jones, Kendall, Ritchie, Robinson & Thorburn, 1978). In 3 animals the fetus was hypophysectomized; the success of the procedure was confirmed by examination of the pituitary fossa and measurements of growth hormone and prolactin in fetal plasma (Jones et al, 1978). Of the remaining 9 animals, 5 gave birth naturally at term and in 4 parturition was induced prematurely by intra-fetal administration of dexamethasone or ACTH,_24 (Synacthen: Ciba Geigy) (Liggins, 1968).…”