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Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU

(Received 21 July 1978)

Prostaglandins of the E and F series have been shown to relax or contract respectively guinea-pig trachea and recently it has been demonstrated that the prostaglandin endoperoxides PGG2 and PGH2 (immediate precursors of prostaglandins E and F) have far greater potency in contracting tracheal smooth muscle than prostaglandin F (Hamberg, Svensson, Hedqvist, Strandberg & Samuelsson, 1976). Furthermore, both thromboxane A2 and prostacyclin can also elicit contraction of the trachea with thromboxane A2 being considerably more active (Omini, Moncada & Vane, 1977; Svensson, Strandberg, Tuvemo & Hamberg, 1977). Administration of thromboxane A2 has been shown to raise the tracheal insufflation pressure in guinea-pigs (Svensson et al. 1977) and indeed its stable metabolite thromboxane B2 is released in relatively large amounts from sensitized guinea-pig lungs when challenged with antigen (Dawson, Boot, Cockerill,

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J. Falconer, J. A. Owens, E. Allotta, and J. S. Robinson


The effect of restricting placental growth on maternal glucose, insulin and placental lactogen was investigated in 16 ewes carrying singleton lambs. Uterine caruncles were removed from seven ewes (caruncle ewes) before pregnancy, resulting in reduced placental size and retarded intra-uterine fetal growth. The concentration of insulin in maternal plasma was similar in both control and caruncle ewes. The concentration of glucose was significantly higher in the caruncle than in the control ewes (3·26 ± 0·15 (s.e.m.) mmol/l, number of observations (n) = 9, vs 2·75 ± 0·1, n = 9, P<0·02, and 3·27 ±0·16, n = 7, vs 2·46± 0·11, n = 12, P<0·001, for the carotid artery and utero-ovarian vein respectively). The concentration of ovine placental lactogen (oPL) in the utero-ovarian vein was reduced in the caruncle compared with the control ewes (283± 65 μg/l, n = and 705±106 μg/l, n = 18, P<0·02, respectively). Restriction of placental growth by removal of endometrial caruncles similarly reduced the concentrations of oPL in maternal arterial plasma (231±54 μg/l, n = 9, and 621±96 μg/l, n = 18, P<0·002). Production of oPL by the placenta was also reduced by limiting placental growth to 30±11 μg/min, n = 8, compared with 133±43 μg/min, n = 15, P<0·05, for the controls. Production of oPL per gram of placenta in the caruncle group, although only 34% of the control value, was not reduced significantly. These observations are consistent with the hypothesis that oPL may be involved in the redirection of maternal glucose during pregnancy to maximize the amount available for the fetus.

J. Endocr. (1985) 106, 7–11

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C. S. Asa, J. A. Robinson, and O. J. Ginther

Daily blood samples from four mares were assayed for cortisol through a total of eight ovulatory cycles. Mean cortisol concentrations on days −14, −13, −10, −9 and −8 before ovulation (dioestrus) were greater than on days −5 to −1 (oestrus). The highest mean (±s.e.m.) value of cortisol occurred on day − 10 (260± 28 nmol/l) and the lowest on day −2 (142 ±14 nmol/l). A single episode on a day in late dioestrus characterized the maximum cortisol value per cycle for five of eight cycles. Extraction of plasma samples with petroleum ether or chromatography before assay, to eliminate interference from progesterone and its metabolites, did not alter the pattern of high dioestrous and low oestrous cortisol concentrations. Maximum follicular diameter at ovulation was negatively correlated with mean cortisol concentration for that cycle. These results indicate that in the mare the adrenals secrete cortisol more actively during dioestrus than during oestrus and suggest that a decline in cortisol values at oestrus may favour full follicular growth and ovulation.

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S. M. Simpson, H. F. Urbanski, and J. E. Robinson

The effects of pinealectomy on a range of photoperiodic responses were investigated in male Japanese quail by measuring plasma LH concentrations in intact, sham-operated and pinealectomized birds in the following four experiments: (1) transfer of sexually quiescent birds from a short photoperiod of 8 h light: 16 h darkness (8L: 16D) to a photostimulatory daylength of 16L: 8D; (2) transfer of sexually mature birds from 16L: 8D to 8L: 16D; (3) castration in 16L: 8D and exposure to 13L: 11D; (4) castration in 8L: 16D and exposure to 13L: 11D. There was no evidence of effects of the pineal gland on the photoperiodically induced changes in LH secretion, the quantitative relationship between LH secretion and photoperiod in intact and castrated birds, or the induction of relative photorefractoriness by prolonged exposure to 16L: 8D. This suggests that there is no pineal influence on the photoperiodic clock or its effectors in this bird.

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The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117 ± 19 (s.e.m.) pg/ml which rose to a mean of 286 ± 63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64 ± 9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.

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The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F (6-oxo-PGF) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.

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J. M. Wallace, J. J. Robinson, S. Wigzell, and R. P. Aitken


It has previously been shown that administration of the indoleamine melatonin to advance the breeding season of ewes is also associated with an increase in ovulation rate and subsequent litter size.

Experiment 1 assessed whether, in ewes receiving melatonin to advance the breeding season, the indoleamine acts directly on the corpus luteum to enhance progesterone secretion or indirectly through increased activity of the hypothalamic pulse generator. Six ewes received 3 mg melatonin orally at 15.00 h daily from 22 March onwards, six were induced to ovulate during mid-anoestrus following withdrawal of a progestagen pessary and injection of exogenous gonadotrophin and six acted as naturally ovulating controls. First overt oestrus occurred between 17 May and 8 July in melatonin-treated ewes, between 21 October and 3 January in control ewes and on 8 July in all induced ewes. On days 2 and 10 after the first overt oestrus, melatonin-treated ewes had pulsatile LH activity characteristic of that measured in control ewes ovulating naturally during the breeding season. There was an absence of any pulsatile LH activity in the induced ewes. Progesterone concentrations between days 7 and 12 following oestrus were significantly higher in melatonin-treated than in control and induced ewes, suggesting a luteotrophic role for melatonin.

Experiment 2 was carried out to determine whether administration of melatonin commencing after induced ovulation and insemination would alter the endocrine status of the ewe and thereby influence the establishment of pregnancy and embryo survival. Thirty-two anoestrous ewes were induced to ovulate on 29 June. Starting 24 h after intra-uterine insemination, 16 ewes were given melatonin daily for 60 days and 16 acted as controls. Daily LH concentrations were higher in melatonin-treated than in control ewes from days 2 to 22 after oestrus, while prolactin concentrations declined in melatonin-treated ewes over the same period. Plasma progesterone concentrations were enhanced in melatonin-treated ewes between days 4 and 9 following oestrus, yet ovulation rates were the same as for controls. Successful pregnancies occurred in 0·56 control (9 of 16) and 0·69 melatonin-treated (11 of 16) ewes. For these ewes the number of fetuses surviving to term as a proportion of ovulation rate was 0·43 and 0·51 for the control and melatonin treatment respectively.

J. Endocr. (1988) 119, 523–530

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Plasma samples from pregnant ewes and their foetuses during the last quarter of gestation were assayed for somatomedin-like activity (SLA) using the porcine costal cartilage assay. In maternal plasma, the mean potency (compared with pooled serum from six sheep) was 0·84 ± 0·05 (s.e.m.) units/ml (n = 15). Somatomedin-like activity in the plasma of five control foetuses (0·91 ± 0·1 units/ml) was similar to the maternal levels and did not change with gestational age. After foetal hypophysectomy the SLA in foetal plasma (0·37 ± 0·05 units/ ml, n = 4) was significantly less than in control animals. In two nephrectomized foetuses, the mean SLA in plasma (0·08 and 0·51 units/ml respectively) was less than in control animals. Retardation of intra-uterine foetal growth was induced by removal of endometrial caruncles before pregnancy in four sheep. The SLA in plasma from these foetuses was 0·38 ± 0·05 units/ml (P< 0·01 v. control animals). The results suggest that SLA in the foetus may be important in the regulation of foetal growth, but they also indicate that factors other than growth hormone may be important in the control of SLA in foetal plasma.

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University of Oxford, Nuffield Institute for Medical Research, and Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford, 0X3 9DS

(Received 10 July 1975)

In sheep and man, parturition is preceded by an increase in the concentration of cortisol in foetal plasma and amniotic fluid respectively (Bassett & Thorburn, 1969; Fencl & Tulchinsky, 1975; Murphy, Patrick & Denton, 1975). In man it has been suggested that cortisol may influence the production of surface active lipids in the foetal lung (see Avery, 1975) and that the foetal adrenal, like that of the sheep, may play a role in the initiation of parturition (see review by Challis & Thorburn, 1975). Because experimental studies are not feasible in man, an animal model would be useful for studies designed to understand the mechanisms and significance of hormonal changes before parturition. We have examined amniotic fluid and maternal plasma cortisol concentrations serially in the

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J A Owens, K L Kind, F Carbone, J S Robinson, and P C Owens


To determine the relationship between placental delivery of oxygen and glucose, circulating insulin-like growth factors (IGFs) and fetal growth, the effect of variable restriction of placental growth was determined in sheep in late gestation. Arterial blood was obtained via indwelling catheters at 120 and 127 days of gestation, prior to necropsy at 130 days to measure fetal and placental weights. Plasma was acidified and subjected to size-exclusion high-performance liquid chromatography at pH 2·8 to dissociate and separate IGFs from their binding proteins. The acid-dissociated IGF fraction was analysed by sensitive and highly specific radioligand assays for IGF-I and IGF-II, previously defined using ovine IGFs. Fetal weight and blood pO2 and glucose at 120 and 127 days of gestation correlated positively with placental weight. Plasma IGF-I was positively associated with fetal weight and fetal liver weight, and with blood pO2 and glucose at both ages. Plasma IGF-II levels also correlated positively with fetal weight, fetal liver weight and with blood glucose and pO2, but only at 127 days of gestation. In the most severely growth-retarded fetal sheep, blood glucose and pO2 and plasma IGF-I were significantly reduced when compared with normal fetuses at 120 days. All decreased further by 127 days of gestation as did plasma IGF-II in severely growth-retarded fetal sheep compared with normal fetuses. These observations are consistent with the hypothesis that both IGF-I and IGF-II are chronically regulated by oxygen and nutrition in utero and mediate part of the influence of placental supply of substrate over fetal growth.

Journal of Endocrinology (1994) 140, 5–13