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Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 253 records · Page 14Linked to original sources

The availability of cortisol in amniotic fluid to the fetus and chorionic and amniotic membranes.

This study examined whether cortisol, present in amniotic fluid (AF), could reach the fetal blood, and might be available to various fetal organs and to the fetal membranes and placenta. [3H]Cortisol ([3H]F) was injected into the AF of five sheep at 130--143 days gestation. Samples of AF and fetal blood were collected for 120 min, at which time the fetuses were delivered and fetal organs and fluid were collected for measurement of the [3H]F content. [3H]F disappeared from AF with an initial half-life of about 40 min and was detected in fetal blood by 30 min after intraamniotic injection. At 120 min after injection, [3H]F was widely distributed within the pregnant uterus, and the highest concentrations of radioactivity were found in allantoic fluid, fetal membranes, and placental tissue. The concentration of [3H]F in the umbilical vein was higher than in umbilical arterial blood in four of five sheep. [3H]F and [3H]cortisone were found in several fetal tissues, including adrenal, kidney, pancreas, lung, and liver. [3H]F in tracheal and stomach fluid was generally less than in fetal blood. We conclude that 1) cortisol can reach the fetus from AF, 2) a major route of entry may be via the vasculature of the fetal membranes, 3) a considerable proportion of [3H]F is retained by the fetal membranes, and 4) interconversion of [3H]F and [3H]cortisone may occur in some fetal tissues.

Amnion↗

Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandin synthesis during pregnancy in the rhesus monkey.

After extra-amniotic treatment of pregnant rhesus monkeys premature parturition was induced in 4 given 2.5 mg PGE-2; none of the 4 monkeys given 100 mg arachidonic acid were affected. The concentrations of PGE, PGF, or 13,14-dihydro-15-oxo-PGF did not change after arachidonic acid treatment, but all increased after PGE-2. It is suggested that the availability of substrate, arachidonic acid, is not a major factor governing the control of PG synthesis but that the latter is suppressed during pregnancy.

Animals↗

Prostaglandins in the sheep fetus: implications for fetal function.

1. In chronically catheterized sheep fetuses, during normal pregnancy, the concentration of PGE in the fetal femoral arterial plasma is invariably greater than that of PGF, and increases during the 12 to 24 hr preceding delivery. The concentration of both PGE and PGF decreases repidly after birth. 2. These changes in fetal prostaglandin levels contrast with the marked increase in PGF, but negligible increase in PGE, in the maternal uteroovarian vein before parturition. 3. The changes in prostaglandin concentrations in fetal plasma at term are associated with only small changes in the concentrations of PGE and PGF in tracheal fluid. In amniotic fluid the concentrations of PGE and PGF increase during the last 4 days in utero. At birth the concentrations of PGE and PGF in fetal urine are similar to the concentrations in amniotic fluid. 4. The concentration of PGE in fetal plasma and in tracheal fluid is significantly elevated for up to 3 days after surgery. The concentration of PGF is significantly elevated in fetal plasma nad tracheal fluid for at least 24 hr after surgery. 5. Three fetuses which were chronically hypoxemic had elevated plasma PGE concentrations in utero. However, acute (1 hr) hypoxia or hypercapnia induced in the fetal lamb by making the ewe breathe appropriate gas mixtures did not produce consistent changes in fetal plasma prostaglandin concentrations. 6. During late pregnancy (day 128) exogenous PGE2 infused at about 1.6 microgram/min for 60 min into the fetal carotid artery achieved concentrations in the fetal femoral artery which were within the physiological range seen at term. At this infusion rate, there was no effect on fetal arterial Po2, Pco2, pH, or hematocrit, and no consistent effect on fetal blood pressure or heart rate. PGE2 infusion had no significant effect on the concentration of growth hormone or prolactin in fetal plasma. Within 30 min after beginning the infusion, however, there was a significant increase in the cortisol concentration in fetal plasma. This effect was seen even at times in pregnancy when the fetal adrenal gland responds only poorly to exogenous or endogenous ACTH.

Amniotic Fluid↗

Conversion of PGE2 to PGF2alpha by fetal sheep blood.

In an attempt to explain the differences in the concentration of primary prostaglandins in the circulation of adult and fetal sheep, we have examined the ability of whole blood from adult and fetal sheep to reduce PGE2 to PGF2alpha in vitro. PGF2alpha was the principal radioactive product formed from 3H PGE2 by both adult and fetal blood. The enzyme initial reaction velocity was significantly higher (P = 0.02) per ml of fetal than adult blood. The optimum enzyme pH (7.0 - 7.5) was similar for both adult and fetal blood. The Km of the enzyme in fetal and adult blood were 3.59 x 10(-7) M and 5.02 x 10(-7) M respectively (P greater than 0.05). There was no detectable metabolism of PGF2alpha by either adult or fetal sheep blood. The results indicate that prostaglandin 9-ketoreductase is present in both adult and fetal sheep blood. Differences in the activity of this enzyme are unlikely to explain the higher concentrations of PGE reported in the plasma of fetal lambs.

Animals↗

Changes in the concentration of cortisol in amniotic fluid after intra-amniotic prostaglandin for midtrimester abortion.

The effects of intra-amniotic prostaglandin E2 (PGE2) and PGF2alpha on the concentration of cortisol in amniotic fluid and in maternal peripheral plasma of patients undergoing abortion between 16 and 23 weeks gestation have been examined. There was a significant (P less than 0-01) increase in the concentration of cortisol in amniotic fluid for hours after PGE2, but not after PGF2alpha. The concentration of cortisol in the maternal peripheral plasma increased in both groups with the progression of abortion, but the levels were not significantly correlated with those in amniotic fluid. These results suggest that by mid-pregnancy fetal cortisol production can be stimulated by PGE2 but the mechanism of this action remains to be elucidated.

Abortifacient Agents↗

Steroids in the amniotic fluid of the rhesus monkey (Macaca mulatta).

Representative C21, C19 and C18 steroids have been measured in the amniotic fluid and maternal femoral plasma of rhesus monkeys during the last 50 days of pregnancy. The concentrations of cortisol, progesterone, androstenedione, oestrone sulphate all increased in amniotic fluid before spontaneous parturition. In contrast, amniotic fluid oestradiol levels remained low and unchanged, and were always less than the concentrations in the maternal plasma. The changes in progesterone, cortisol and oestrone concentrations in amniotic fluid occurred independently of significant changes in the concentration of these steroids in the maternal plasma. Betamethasone administered to monkeys after day 150 of pregnancy suppressed amniotic fluid and maternal plasma cortisol. This treatment markedly suppressed the concentration of progesterone in amniotic fluid, but did not alter its concentration in maternal plasma. It is concluded that during late pregnancy in the rhesus monkey there is an increase in the concentration of some steroids in amniotic fluid independent of alterations in their concentrations in maternal plasma. These changes could reflect an increase in foetal adrenal steroid secretion.

Amniotic Fluid↗

Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.

Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.

Adrenocorticotropic Hormone↗