Search PubMed⌕ Search

Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 271 records · Page 15Linked to original sources

Prostaglandins in the circulation of the fetal lamb.

Prostaglandin E and PGF have been measured in the plasma of chronically catheterized fetal lambs throughout the last 20-35 days (0.73 onwards) of gestation. The mean concentration of PGE was higher than that of PGF. There was a significant increase in the concentration of PGE but little change in the concentration of PGF in samples of fetal plasma taken within 24 h of parturition. In contrast, at this time in maternal utero-ovarian venous plasma, there was a large increase in PGF, but relatively little change in PGE. There was a significant decrease in the concentration of PGE and PGF in the plasma of lambs within 12 h after birth compared to the levels found in the same animals as fetuses a few hours previously. The physiological importance of these changes is discussed.

Animals↗

Production of prostaglandin Falpha in ewes following luteal regression induced with a prostaglandin analogue, Estrumate (cloprostenol; I.C.I. 80996).

A single injection (100 mug i.m.) of Estrumate (I.C.I. 80996) was used to induce luteal regression on day 8 of the estrous cycle in 3 sheep. Progesterone levels in the utero-ovarian vein and femoral artery had fallen within 6 h to less than 50% of the concentrations seen before injection of the analogue. Luteolysis was not associated with endogenous production of PGF. The concentration of PGF in the uteroovarian vein began to increase 27-39 h after the administration of Estrumate, reaching a mean maximum concentration of 1455pg/ml 48 h after Estrumate. The mean concentration of PGF in the utero-ovarian vein between 36-69 h after Estrumate was significantly greater than during the 24 h before Estrumate (control period) or during the 0-30 h immediately after injection (both P less than 0.001). The maximum secretion of estradiol and the pre-ovulatory LH peak occurred during the period of elevated PGF concentrations in the utero-ovarian veins. The possible importance of endogenous PGF production at this time is discussed.

Animals↗

Metabolic clearance rate and production rate of oestradiol in conscious rabbits.

A continuous isotope infusion technique was used to measure the metabolic clearance rate (MCRB) and production rate (PRB) of oestradiol-17beta in a group of six non-pregnant conscious Chinchilla rabbits. The mean MCRB of oestradiol was 162 ml/min (0 X 079 1/min/weight0 X 75), and at equilibrium a significant proportion of the radioactivity in the circulation was present as oestrone (conversion ratio oestradiol to oestrone, 27 X 6%). The mean PRB of oestradiol was 4 X 3 ng/min, which is equivalent to about 5 mug/day. Some day-to-day variation was seen in the endogenous concentrations of oestradiol, oestrone and progesterone although in general the levels of the two oestrogens were less than 30-40 pg/ml, and progesterone levels were below 300 pg/ml apart from short peaks up to 600 pg/ml. These values were compared with previous measurements of the ovarian secretion rate of oestradiol measured directly in anaesthetized animals.

Animals↗

Production of prostaglandins E and Falpha by corpora lutea, corpora albicantes and stroma from the human ovary.

This study has shown that corpora lutea, stromal tissue and corpora albicantes from human ovaries contain prostaglandin E (PGE) and PGFalpha, and that the two former tissues can synthesize these prostaglandins during incubation. Enhanced syntheses, especially of PGE, occurred on adding arachidonic acid to the incubation medium, and the presence of prostaglandin synthetase activity was conclusively demonstrated. In corpora lutea obtained during the early and mid-luteal phase, the mean concentrations of PGE and PGFalpha were 34.3 and 9l9 ng/g respectively (mean ratio PGE:PGFalpha = 3.7); similar values were found in three corpora lutea from women at 10-12 weeks of pregnancy. All these corpora lutea contained appreciable amounts of progesterone and oestradiol-17beta. Prostaglandin levels were generally lower in corpora lutea obtained during the late luteal phase, although the PGE:PGFalpha ratio had increased to a mean value of 8.4. In corpora albicantes, the concentrations of both PGE and PGFalpha were significantly higher than the levels found in corpora lutea (P less than 0.01), whilst the mean ratio of PGE:PGFalpha had fallen significantly to 1.8 (P less than 0.01). Prostaglandin levels in stromal tissue varied considerably between individuals. The mean values were significantly lower than those of the corpora albicantes (P less than 0.01) but not significantly different to corpora lutea at any stage. These findings are discussed in relation to the possible role of prostaglandins in ovarian steroidogenesis and corpus luteum regression in man.

Adult↗

Prostaglandins in the plasma and amniotic fluid of rhesus monkeys during pregnancy and after intra-uterine foetal death.

Prostaglandin F (PGF) was measured in amniotic fluid, and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) was measured in maternal peripheral venous plasma and amniotic fluid of rhesus monkeys during late pregnancy. 13,14-Dihydro-15-keto-PGF2 alpha was determined in the maternal peripheral venous plasma of two animals following intra-uterine foetal death. The mean concentration of PGF and PGFM in amniotic fluid increased fourfold during the last 5 days of pregnancy. This increase was associated with an increase in the oestrone concentration in amniotic fluid and in maternal plasma. In normal pregnancy there was no increase in PGFM levels in the maternal peripheral vein, up to 1-2 days pre partum. After intra-uterine death, progesterone concentration in the maternal peripheral vein was unaltered, but oestrone and oestradiol declined. In plasma samples taken within 12 h of delivery, the concentration of PGFM was raised. It is concluded that an increase in prostaglandin production accompanies delivery at normal term, and at delivery past term following intra-uterine foetal death.

Amniotic Fluid↗

The effects of dexamethasone on the peripheral plasma concentrations of androstenedione, testosterone and cortisol in the pregnant rhesus monkey.

The concentrations of androstenedione, testosterone and cortisol have been measured in the maternal peripheral plasma of normal pregnant rhesus monkeys (Macaca mulatta), and in rhesus monkeys treated daily with dexamethasone during late pregnancy. During the last 30 days of pregnancy, the mean plasma concentrations of androstenedione, testosterone and cortisol were about 1400-2000 pg/m1375-425pg/ml and 300-400 ng/ml, respectively. None of these steroids increased significantly before parturition. As there was no rise in maternal androgens in late pregnancy when plasma estrogens increase sharply, it suggested that his elevation of plasma estrogens is related to an increase of fetal precursors Dexamethasone treatment resulted in 90% suppression of plasma cortisol and 40%-60% suppression of androstendione and testosterone. As the suppression of maternal androgens was of lesser magnitude than the decline of plasma estrogens, and as the androgens did not continue to fall with continuing dexamethasone treatment as did the estrogens, these findings also suggest that the decline in plasma estrogens is related in large part to suppression and atrophy of the fetal adrenals.

Androstenedione↗

The effects of dexamethasone and indomethacin on the outcome of pregnancy in the rabbit.

Pregnant rabbits were treated with indomethacin (8-10 mg/kh/day) or dexamethasone (1-2-1-8 mg/kh/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation was studied. Treatment with indomethacin significantly prolonged the length of gestation (P smaller than 0-01) compared iwth control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatemnt reliably induced premature delivery within 3-6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF. These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.

Administration, Oral↗