Biomedical subjects

A L Fowden

Publications and source records attributed to A L Fowden.

At least 109 records · Page 6Linked to original sources

PubMed1993

Insulin deficiency: effects on fetal growth and development.

Insulin deficiency in either the mother or foetus has significant effects on fetal growth and development. In the human, maternal insulin deficiency, or diabetes mellitus, leads to macrosomia and increased adiposity of the foetus, while specific fetal hypo-insulinaemia is associated with intra-uterine growth retardation. When maternal diabetes is induced in experimental animals, no consistent increases in fetal bodyweight are observed although the body fat content of the foetus is increased in the majority of species studied. The magnitude of the fetal weight gain during maternal diabetes appears to be determined by the body fat content of the foetus, the severity and duration of the diabetes and by the temporal pattern of maternal hyperglycaemia observed during pregnancy. The latter factors, in particular, influence the level of insulin in the foetus which, in turn, regulates the rate of intra-uterine growth. By contrast, fetal insulin deficiency has a more uniform effect on fetal growth and leads to impaired growth in both experimental and naturally occurring hypo-insulinaemic conditions. Fetal insulin deficiency reduces fetal growth by decreasing nutrient uptake and utilization of the fetal tissues and by altering the circulating concentrations of the insulin-like growth factors. Consequently, deficiencies in either fetal or maternal insulin secretion during pregnancy can alter fetal growth and have important consequences for perinatal survival and postnatal morbidity.

Animals↗

PubMed1993

Insulin-like growth factor-II messenger ribonucleic acid expression in fetal tissues of the sheep during late gestation: effects of cortisol.

Using RNase protection analysis, insulin-like growth factor-II (IGF-II) mRNA levels were measured in various tissues from fetal sheep during late gestation (term, 146 +/- 2 days) and after experimental manipulation of fetal plasma cortisol levels. No gestational trend in IGF-II mRNA levels was observed in the fetal lung, kidney, or skeletal muscle. However, in the fetal liver, there was a marked decline in IGF-II mRNA abundance immediately before term, which closely paralleled the normal prepartum surge in fetal plasma cortisol. This decrease in hepatic IGF-II mRNA levels toward term was prevented when the cortisol surge was abolished by fetal adrenalectomy and was stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Hepatic and renal IGF-II mRNA abundances were also reduced when fetal cortisol levels were raised endogenously by maternal fasting in late gestation. Muscle IGF-II mRNA levels were reduced by fetal cortisol infusion, but not by maternal fasting, and were higher in adrenalectomized than in intact fetuses in late gestation. No change in IGF-II mRNA levels were observed in the fetal lung in response to altering the fetal cortisol level either exogenously or endogenously. When the data from all fetuses were combined regardless of treatment or gestational age, there was a significant inverse correlation between the plasma cortisol level in utero and IGF-II mRNA abundance in the fetal liver (P < 0.001), but not in any of the other fetal tissues studied. These findings show that cortisol suppresses IGF-II gene expression in the liver of the sheep fetus and indicate that the developmental change in hepatic IGF status toward term may be due to the prepartum cortisol surge.

Adrenal Glands↗

PubMed1993

The effects of cortisol on hepatic and renal gluconeogenic enzyme activities in the sheep fetus during late gestation.

The effects of cortisol on hepatic and renal gluconeogenic enzyme activities were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol. Hepatic and renal gluconeogenic enzyme activities increased with increasing gestational age in parallel with the normal rise in fetal cortisol levels towards term (146 +/- 2 days). For the majority of enzymes this increase in activity towards term was prevented when the prepartum cortisol surge was abolished by fetal adrenalectomy and stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log plasma cortisol concentration in utero and the activities of glucose-6-phosphatase, fructose diphosphatase, phosphoenolpyruvate carboxykinase and aspartate transaminase in the fetal liver and kidney, and pyruvate carboxylase in the fetal liver but not in the kidney. No correlation was observed between log plasma cortisol and alanine aminotransferase activity in either fetal liver or kidney. These findings show that cortisol is a physiological regulator of most of the fetal gluconeogenic enzymes and enhances the glucogenic capacity of the sheep fetus during late gestation.

Adrenalectomy↗

PubMed1992

The effects of glycemia on breathing movements and plasma prostaglandin E concentrations in the sheep fetus.

OBJECTIVE: The purpose of this study was to determine the roles of fetal plasma glucose and prostaglandin E in controlling fetal breathing movements. STUDY DESIGN: Five late pregnant ewes with catheterized twin fetuses were fasted for 48 hours; one fetus was kept normoglycemic (by glucose infusion) and the other allowed to become hypoglycemic during this period. Fetal breathing movement and fetal and maternal plasma prostaglandin E and glucose concentrations were measured throughout. Data were analyzed by paired and unpaired t tests. RESULTS: The mean incidence of fetal breathing movement was significantly greater in the normoglycemic fetuses that in the hypoglycemic twins at the end of the fast (p less than 0.05), whereas plasma prostaglandin E levels increased significantly (p less than 0.05) and to the same extent in both groups of fetuses. CONCLUSION: The reduced incidence of ovine fetal breathing movement that occurs during maternal fasting appears to be primarily caused by fetal hypoglycemia and does not directly involve changes in fetal plasma prostaglandin E.

Animals↗

PubMed1992

Intravenous catheterisation of foetus and mare in late pregnancy: management and respiratory, circulatory and metabolic effects.

The uterine and umbilical vessels of 12 pregnant ponies were catheterised to study foetal metabolism. The effects of this procedure on maternal and foetal cardiovascular, respiratory, metabolic and adrenocortical activity were monitored during and after surgery. Premedication with acepromazine-butorphanol-detomidine was followed by induction of anaesthesia with detomidine and ketamine and maintenance, using mechanical ventilation, with halothane in oxygen and nitrous oxide. Mean maternal arterial blood pressure was greater than 70 mmHg during anaesthesia and arterial oxygen tension remained over 100 mmHg. The foetuses were adequately oxygenated but were hypercapnic and lactic acidaemic. Most maternal and foetal blood gases and metabolites had returned to normal by 24 h, although foetal plasma lactate fell more slowly. The maternal adrenocortical discharge was less severe than reported previously and plasma cortisol had fallen to basal levels by 48 h after surgery. Foetal plasma cortisol remained low and did not change during or after surgery. Arterio-venous metabolite and gas tension differences across the uterine and umbilical circulations were slightly greater at operation than in the recovery period, suggesting that uteroplacental perfusion may have been impaired during surgery. Post-operative recovery of the mare and foetus was satisfactory and subsequent problems associated with the foetal catheters were not related to the anaesthesia or surgery.

Acid-Base Equilibrium↗

PubMed1992

The development of gluconeogenic enzymes in the liver and kidney of fetal and newborn foals.

The activities of glucose-6-phosphatase (G6P), fructose diphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), aspartate and alanine transferases were measured in liver and kidney of fetal foals between 100-318 days of gestation (term approximately 335 days) and during the immediate postnatal period (0-48 h after birth). All 5 enzymes could be detected in the fetal liver and kidney at the youngest gestational age studied. Mean fetal activities were lower than those observed in their mothers and showed no change with gestational age for the majority of enzymes studied. However, renal PEPCK and renal and hepatic G6P did increase towards term. At birth, hepatic and renal activities of these two enzymes were higher than those found in late gestation or in the adult animals. There was no apparent change in the activities of any of the other enzymes at birth. In late gestation (80-90% gestation), the activities of G6P and PEPCK in the foal were low compared to those in other species at the same stage of gestation. Similarly, the perinatal increase in enzyme activity occurred closer to term in the foal than in most other species. These observations indicate that maturation of glucogenic capacity occurs relatively late in the fetal foal and suggests that this process may be dependent on the prepartum rise in fetal cortisol as occurs in other species.

Aging↗

PubMed1991

Physiological and pathological influences on sheep blood plasma amine oxidase: effect of pregnancy and experimental alloxan-induced diabetes mellitus.

A copper-containing amine oxidase is present in sheep blood plasma and has a high capacity to deaminate spermine and spermidine. The physiological function of this enzyme remains to be determined. Sheep blood plasma amine oxidase (SPAO) was measured by its ability to deaminate spermidine (700 microM) using a peroxidase-linked colorimetric assay developed for microtitre plates. SPAO activity has been studied in a group of Welsh Mountain sheep with experimental alloxan-induced diabetes. This resulted in an increase in SPAO activity which reached a peak of 70 days after alloxan treatment (60 per cent increase). This change could be seen in both pregnant and non-pregnant diabetic sheep. In normal pregnant ewes, SPAO activity remained stable for the first 100 days of pregnancy but declined by 50 per cent in the last month of pregnancy. Together, these findings suggest that SPAO activity is controlled by hormonal influences. This sensitive and convenient assay method could provide clues as to the physiological significance of SPAO and may be a useful clinical chemical indicator in the sheep.

Amine Oxidase (Copper-Containing)↗

PubMed1991

Induction of labour in sheep by inhibition of 3-beta hydroxysteroid dehydrogenase: role of the fetal adrenal.

In sheep parturition may be induced within 33 h in late gestation by inhibiting progesterone production with the 3 beta hydroxysteroid dehydrogenase inhibitor Epostane. Its effect has now been investigated in ewes carrying adrenalectomised (n = 5), hypophysectomised (n = 4) or intact (n = 5) fetuses to determine the role of the fetal adrenal during this type of maternally-induced delivery. Epostane was infused i.v. (1.5 mg/kg) into each group of ewes at 137-156 days gestation. Fetus and mother were sampled from the time of administration until delivery. Measurements of plasma ACTH, cortisol, progesterone and PGF2 alpha metabolite (PGFM) were made and intrauterine pressure was monitored. Epostane induced delivery significantly later in the adrenalectomised (44 h) and hypophysectomised (52 h) animals compared with the controls (33 h). The drop in maternal plasma progesterone was similar in all 3 groups, but the subsequent increases in arterial and uterine venous PGFM were smaller in the adrenalectomised and hypophysectomised ewes than in the controls. The large escalation in fetal plasma cortisol before birth in controls was absent in adrenalectomised and hypophysectomised fetuses. The slight rises in plasma cortisol observed in the latter from about 24 h after Epostane, were related to the concomitant increases in maternal plasma levels (r = 0.76, P less than 0.01). No fetuses became hypoxic or acidotic during the period of induction despite the prolonged labour of hypophysectomised and adrenalectomised fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

PubMed1991

Tissue glycogen and glucose 6-phosphatase levels in fetal and newborn foals.

Glycogen and glucose 6-phosphatase levels were measured in a variety of tissues from fetal, newborn and adult pregnant mares. Hepatic and renal glucose 6-phosphatase activities increased with increasing gestational age and rose further in the 24 h after birth to values similar to those observed in maternal tissues. The glycogen content of fetal liver and skeletal muscle also increased in late gestation, whereas that of fetal lung and cardiac muscle decreased toward term. No significant change in renal glycogen content with fetal age was observed. The values of hepatic glycogen and glucose 6-phosphatase found in the fetal foal near term were less than those observed previously in fetal sheep and pigs at a similar stage of gestation. These observations suggest that, in late gestation, the fetal foal has a limited glucogenic capacity compared with other domestic species and may have difficulty maintaining an adequate glucose supply during adverse conditions.

Animals↗

PubMed1991

Studies of bone marrow and leucocyte counts in peripheral blood in fetal and newborn foals.

Clinical and pathological records of 124 foals were studied. The foals were assigned to six groups; normal, premature, dysmature, bacterially infected, neonatal maladjustment syndrome and Equid herpesvirus type 1 (EHV-1) infected. Also, 6 pony fetuses were sampled via catheters in the umbilical vein and artery between 280 and 310 days gestation. Bone marrow aspiration was performed on a further 14 foals. Premature foals had significantly lower neutrophil counts than normal foals up to 5 h. Foals with bacterial infections had significantly lower neutrophil counts up to age 12 h. EHV-1 infected foals had significantly lower neutrophil counts up to age 24 h and significantly lower lymphocyte counts than all other groups up to age 12 h. Premature foals showed a higher neutrophil count and neutrophil/lymphocyte (N:L) ratio in survivors compared with non-survivors when all ages were considered, although the differences were not significant before 35 h. Discriminant analysis showed a 99% chance that the EHV-1 group could be identified from all other groups except dysmature foals, where discrimination between the two groups was about 90%. In catheterized fetuses, age-related increases in neutrophil counts and the N:L ratio occur from 280 to 310 days of gestation. In one preparation available for study leading up to parturition, the N:L ratio widened during the 3 days pre-partum. The bone marrow aspirates showed no significant changes in the myeloid:erythroid (M:E) ratio during the first 4 days post partum. The left shift (LS) index was significantly higher in foals suffering bacterial infection compared with normal or dysmature foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Relationship between circulating tri-iodothyronine and cortisol in the perinatal period in the foal.

Pre- and post partum changes in plasma T3 have been examined in relation to plasma cortisol in 23 newborn foals (12 full term, 6 premature and 5 'twilight'), and in 5 fetuses catheterized in late gestation. Blood samples were collected daily from the fetuses and from the neonates at 30-min intervals for 2 h after birth; the plasma was assayed for T3 and cortisol by standard radioimmunoassay methods. In the full-term foals, plasma cortisol and T3 concentrations were high at birth (67.4 +/- 6.1 and 4.3 +/- 0.3 ng/ml respectively) and rose to a maximum during the following 2-h period to 141.0 +/- 8.8 ng/ml and 8.4 +/- 0.5 ng/ml. The corresponding changes in the premature foals over the same period were significantly lower (P less than 0.01; 17.2 +/- 2.2 to 27.0 +/- 4.3 ng cortisol/ml and 2.9 +/- 0.5 to 5.4 +/- 0.6 ng T3/ml). In the 'twilight' group, intermediate increases in both cortisol and T3 were observed. In the 5 chronically catheterized fetuses, both plasma cortisol and T3 were low in the last few weeks of gestation (7.0 +/- 1.1 ng/ml and 1.2 +/- 0.2 ng/ml respectively). In 2 fetuses there was little or no increase in plasma cortisol or T3 before induction of labour at about 320 days; one foal was premature and the other 'twilight'. Infusion of adrenocorticotrophic hormone for 4.5 days into the third fetus from 309 days led to an increase in both cortisol and T3 and the birth of a viable, full term foal. The 2 remaining fetuses were delivered spontaneously, one at term and one at 300 days (well before term). The latter was viable but dysmature; it showed a slight prenatal rise in plasma cortisol with little change in T3. When all the data were combined from both fetuses and neonates a significant positive correlation between plasma T3 and cortisol was found (P less than 0.001). These results demonstrate a relationship between circulating cortisol and T3 in the perinatal period and show that prematurity is associated with low concentrations of both hormones.

Adrenocorticotropic Hormone↗

PubMed1991

Respiratory and non-respiratory thoracic movements in the fetal pig.

The aim of this study was to characterize the pre-natal activity of the respiratory muscles in a non-ruminant, the pig. Tracheal pressure was recorded from 11 unanaesthetized fetal pigs in utero during late gestation in 9 sows. Two types of inspiratory effort occurred episodically in each fetus during each recording period. Episodes of breathing movements lasted 8.6 +/- 1.1 min and their overall incidence was 41.1 +/- 3.4% of recording time. The mean amplitude of the respiratory efforts was 7.6 +/- 1.1 mmHg and the mean inspiratory time was 0.8 +/- 0.1 s. Episodes of non-respiratory inspiratory efforts, considered to be fetal hiccups, lasted 5.6 +/- 0.8 min. Individual hiccups had a duration of 150-200 msec, a mean amplitude of 41.4 +/- 2.4 mmHg and a mean frequency, during episodes, of 21.9 +/- 2.0 min-1. In contrast to fetal breathing movements, hiccups appeared to be stereotyped events. It is concluded that, in common with other ruminant and non-ruminant species, two types of inspiratory effort occur in the fetal pig. Fetal hiccups, which have been observed in non-ruminant species, may be analogous to deep inspiratory efforts in the sheep fetus. The stimulus for, and function of, fetal hiccupping remain to be determined.

Animals↗

PubMed1991

Plasma progestagens in the mare, fetus and newborn foal.

This study used gas chromatography/mass spectrometry (GC/MS) to identify and measure plasma progestagens. The method included deuterated internal standards, e.g. [17,21,21,21-2H]-5 alpha-pregnane-3,20-dione, solid-phase extraction, derivatization (methoxime/t-butyldimethylsilyl) and GC/MS. Full-scan screening identified 3 5-pregnenes, 2 4-pregnenes and 7 5 alpha-pregnanes (no 5 beta-pregnanes). The selected ion mode was used for routine quantitation from calibration curves; response was linear (r greater than 0.98) from 2 to 2000 ng equivalents/ml (0.5 ng/ml method sensitivity) and intra- and inter-assay coefficients of variation were less than 20%. The predominant steroids in plasma from pregnant pony and light-horse mares near term were 20 alpha-hydroxy-5 alpha-pregnan-3-one (400-2100 ng/ml) and 5 alpha-pregnane-3 beta,20 alpha-diol (100-350 ng/ml). Four other mono- and dihydroxy-5 alpha-pregnanes were generally between 30 and 100 ng/ml. These pregnanes were detectable initially between 30 and 60 days gestation and increased gradually until a more rapid increase was observed 30 days pre-partum. Maximum concentrations occurred during the last 2-3 days, followed by a decline before parturition. The progesterone profile during early pregnancy was similar to that given in previous reports. However, progesterone was not detectable during mid- to late pregnancy, except in a few mares near term (0.5-1 ng/ml). 5 alpha-Pregnane-3,20-dione (5 alpha-DHP) concentrations were similar to those of progesterone during early pregnancy but remained elevated and relatively constant (30 ng/ml) to term. No 20 alpha- or 20 beta-hydroxy-4-pregnen-3-one was detected in mare plasma. In mares that aborted or delivered prematurely, these pregnanes showed a profile of decreasing concentrations. In the fetal artery (250-300 days) plasma concentrations (ng/ml) of the predominant steroids were: pregnenolone (422), 5-pregnene-3 beta,20 beta-diol (171), 3 beta-hydroxy-5 alpha-pregnan-20-one (277) and 5 alpha-pregnane-3 beta,20 beta-diol (221). In the fetal vein, the predominant steroid was 5 alpha-DHP (205); progesterone was low (12.7 ng/ml) but consistently found. Steroids in the uterine venous plasma were similar in type and concentrations to those found in the peripheral circulation; uterine arterial concentrations were generally 50% lower. These results suggest that fetal pregnenolone is converted rapidly to progesterone and/or 5 alpha-DHP by the placenta, with further 3 beta- and 20 beta-hydroxylation by the fetus. In contrast, 20 beta-hydroxylation predominated on the maternal side and so may not directly reflect the fetal-placental environment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Production of 5 alpha-dihydroprogesterone during late pregnancy in the mare.

Changes in the progesterone metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) in maternal plasma in late gestation, and possible sites of production of this steroid were studied in pony and Thoroughbred mares by an enzyme-linked immunosorbant assay for 5 alpha-DHP. In Thoroughbred mares, plasma 5 alpha-DHP increased from 63.7 +/- 10.5 ng/ml (27 days pre-partum) to 161.7 +/- 30.8 ng/ml (1 day pre-partum) falling to 90.2 +/- 16.1 ng/ml on the day of parturition. In pony mares, values rose from 30.8 +/- 8.1 ng/ml (27 days pre-partum) to 79.1 +/- 30.8 ng/ml (3 days pre-partum) and then decreased to 28.2 +/- 7.1 ng/ml on the day of parturition. Concentrations of 5 alpha-DHP were greater in the umbilical and uterine veins than in the corresponding umbilical and uterine artery samples. Tissues incubated with isotopically-labelled substrates showed that the fetal placenta converted pregnenolone to progesterone (47.5 +/- 9.0%). Endometrium metabolised [3H]pregnenolone to progesterone and 5 alpha-DHP (11.0 +/- 3.0% and 7.8 +/- 2.4%, respectively), and [14C]progesterone to 5 alpha-DHP (9.3 +/- 2.5%). Deuterium-labelled substrates were used to confirm the identity of these products by gas chromatography-mass spectrometry. Negligible amounts of 5 alpha-DHP were formed by other fetal tissues (adrenal, liver, kidney and testis). The results show that 5 alpha-DHP production in late pregnancy is derived primarily from endometrial metabolism of pregnenolone and/or progesterone.

5-alpha-Dihydroprogesterone↗

PubMed1990

Endocrine regulation of tissue glucose-6-phosphatase activity in the fetal sheep during late gestation.

Endocrine regulation of tissue glucose-6-phosphatase activity in utero was examined by measuring enzyme levels in liver and kidneys of fetal sheep during the second half of gestation and after experimental manipulation of fetal plasma cortisol and insulin levels. Tissue glucose-6-phosphatase activities increased toward term in parallel with the rise in fetal plasma cortisol. At birth, the activities were significantly higher than in utero, but significantly less than in adult nonpregnant sheep. Fetal hypophysectomy lowered fetal plasma cortisol and reduced hepatic and renal glucose-6-phosphatase activities compared with those in intact fetuses near term. Conversely, intrafetal cortisol infusion raised fetal plasma cortisol and significantly increased tissue glucose-6-phosphatase activity to values similar to those in older fetuses. When the data from these groups of fetuses and the newborn lambs were combined, there was a significant positive correlation between the plasma cortisol level and the glucose-6-phosphatase activity in both liver and kidney. Fetal hypoinsulinemia was induced by fasting the ewe for 48 h and by fetal pancreatectomy. Fetal hepatic and renal glucose-6-phosphatase activities were higher in fasted than in fed animals, while pancreatectomy had little apparent effect on enzyme activity in either tissue. However, when differences in plasma cortisol were taken into account, hepatic, but not renal, glucose-6-phosphatase activities were higher in both groups of hypoinsulinemic fetuses than would have been observed in normoinsulinemic animals with a similar plasma cortisol level. Partial correlation analysis of the data showed that plasma insulin and cortisol were both significant influences on hepatic glucose-6-phosphatase activity in utero, but plasma cortisol had the more pronounced effect. Cortisol, therefore, appears to be a physiological regulator of tissue glucose-6-phosphatase activity in utero and enhances the glucogenic capacity of the sheep fetus during late gestation.

Animals↗

PubMed1989

The effects of streptozotocin on rates of glucose utilization, oxidation, and production in the sheep fetus.

Streptozotocin was injected into chronically catheterized, late gestation fetal sheep to produce hypoinsulinemia and to investigate the effects of hypoinsulinemia on the rates of utilization and production of glucose. Each fetus received two IV doses of streptozotocin (100 mg/kg estimated fetal weight per dose). Experiments were conducted before and five to six days after giving the streptozotocin. Experiments consisted of direct measurement of fetal glucose utilization rate (using [U-14C]glucose tracer) and umbilical glucose uptake rate (Fick principle) during basal and glucose infusion periods. Fetal endogenous production rate was calculated as the difference between rates of fetal glucose utilization and umbilical glucose uptake. Following streptozotocin injections the rate of fetal glucose utilization was reduced (5.50 +/- 0.34 to 4.13 +/- 0.32 mg/kg/min) as was the rate of fetal CO2 production from fetal glucose carbon oxidation (91.7 +/- 5.3 to 71.7 +/- 6.0 mumol/kg/min) and the rate of fetal glucose oxidation (2.75 +/- 0.16 to 2.15 +/- 0.18 mg/kg/min). At the same time the rate of fetal endogenous glucose production was enhanced (0.31 +/- 0.18 to 2.06 +/- 0.28 mg/kg/min). These changes in glucose metabolism were accompanied by hypoinsulinemia (16 +/- 2 to 8 +/- 1 muU/mL), an inhibition of insulin secretion in response to glucose infusion (16 +/- 2 to 34 +/- 2 muU/mL control, 8 +/- 1 to 9 +/- 1 muU/mL after streptozotocin), hyperglycemia (19.5 +/- 0.7 to 30.4 +/- 1.7 mg/dL), and a reduction in the rate of umbilical glucose uptake (5.19 +/- 0.34 to 2.07 +/- 0.40 mg/kg/min). The disturbances in glucose metabolism could be alleviated only in part by insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Pituitary-adrenocortical activity in the fetal pig in the last third of gestation.

The responsiveness of the fetal adrenal to a rise in either endogenous or exogenous ACTH (adrenocorticotrophic hormone) was examined acutely in piglets between 70 and 105 days gestation (term, 115 days). In addition the pre-partum changes in plasma ACTH and cortisol were followed in chronically catheterized fetuses and the effect of a continuous intrafetal ACTH infusion on the time of delivery was also investigated. The acute experiments on ten sows were carried out (under sodium pentobarbitone) on twenty-five fetuses, sampled from a branch of the umbilical artery with minimal disturbance. A second sample was taken 10-20 min later after exteriorization or surgery (catheterization). Such fetal manipulation resulted in significant increases in plasma ACTH and cortisol from 70 days gestation and the responses increased with fetal age. No corresponding changes were seen in the controls or in the sow over the same period. An exogenous bolus of ACTH (200 ng ml-1 I.V.) evoked rises in fetal plasma cortisol comparable with the endogenous changes (+11 +/- 2 ng ml-1, n = 4). Chronic experiments were carried out on fourteen sows catheterized under sodium pentobarbitone anaesthesia at 95-100 days gestation; in fetuses sampled until delivery (at 111-114 days) gradual rises in both fetal plasma cortisol and ACTH were observed. There was a highly significant positive correlation between plasma cortisol and log plasma ACTH (r = 0.81, n = 52, P less than 0.001). Analysis of the basal values from the 70-100 day fetuses also showed a positive correlation (r = 0.47, n = 23, P less than 0.05) but the slope of the regression line was significantly less than that for the older fetuses indicating a greater adrenocortical response to a given level of ACTH nearer term. In five sows a continuous infusion of ACTH (0.125 mg day-1 for 4-5 days from about 100 days) was given to one or two fetuses per litter (total size, 7-12). This treatment resulted in a rise in fetal plasma cortisol to 85.4 +/- 8.9 ng ml-1, which was equivalent to that found during labour, but did not induce premature parturition.

Adrenocorticotropic Hormone↗

PubMed1989

The effects of insulin on the growth rate of the sheep fetus during late gestation.

The effects of insulin on fetal growth rates were investigated by measuring crown-rump length (CRL) chronically in sheep fetuses before and after pancreatectomy, sham operation or pancreatectomy accompanied by insulin-replacement treatment. Pancreatectomy of the fetus produced hypoinsulinaemia and reduced the daily and total increments in CRL by 40-50% over the last 20-30 days of gestation. The growth rate fell immediately after pancreatectomy and remained low throughout the rest of gestation. In contrast to the sham-operated fetus no pre-partum decline in the growth rate was observed in the pancreatectomized animal. The body weight, limb lengths and actual CRL at delivery were also significantly less after pancreatectomy than in the sham-operated animals. When fetal insulin levels were maintained after pancreatectomy by exogenous insulin infusion, the daily and total increments in CRL and the body size at delivery were restored to their normal values. Raising insulin levels above normal in the pancreatectomized fetus did not lead to additional fetal growth. When the data from all the fetuses were combined irrespective of treatment, there were significant positive correlations between the plasma insulin concentration in utero and the mean daily increment in CRL after treatment and between the former value and the body weight at delivery. These observations demonstrate that insulin is a major determinant of the growth rate in utero and that it is required throughout late gestation for the normal growth and development of the sheep fetus. They also indicate that insulin deficiency is probably the primary cause of the growth retardation observed after fetal pancreatectomy.

Animals↗