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Biomedical subjects

M H Oliver

Publications and source records attributed to M H Oliver.

At least 19 recordsLinked to original sources
PubMed2006

Fetal exposure to excess glucocorticoid is unlikely to explain the effects of periconceptional undernutrition in sheep.

Periconceptional undernutrition alters fetal growth, metabolism and endocrinology in late gestation. The underlying mechanisms remain uncertain, but fetal exposure to excess maternal glucocorticoids has been hypothesized. We investigated the effects of periconceptional undernutrition on maternal hypothalamic-pituitary-adrenal axis function and placental 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) activity. Ewes received maintenance feed (N, n= 20) or decreased feed from -60 to +30 days from mating to achieve 15% weight loss after an initial 2-day fast (UN, n= 21). Baseline plasma samples and arginine vasopressin (AVP)-corticotrophin-releasing hormone (CRH) challenges were performed on days -61, -57, -29, -1, +29, 33, and 49 from mating (day 0). Maternal adrenal and placental tissue was collected at 50 days. Baseline plasma levels of adrenocorticotrophic hormone (ACTH) and cortisol decreased in the UN group (P < 0.0001). ACTH response to AVP-CRH was greater in UN ewes during undernutrition (P= 0.03) returning to normal levels after refeeding. Cortisol response to AVP-CRH was greater in UN ewes after the initial 2-day fast, but thereafter decreased and was lower in UN ewes from mating until the end of the experiment (P= 0.007). ACTH receptor, StAR and p450c17 mRNA levels were down-regulated in adrenal tissue from UN ewes. Placental 11betaHSD2 activity was lower in UN than N ewes at 50 days (P= 0.014). Moderate periconceptional undernutrition results in decreased maternal plasma cortisol concentrations during undernutrition and after refeeding, and adrenal resistance to ACTH for at least 20 days after refeeding. Fetal exposure to excess maternal cortisol is unlikely during the period of undernutrition, but could occur later in gestation if maternal plasma cortisol levels return to normal while placental 11betaHSD2 activity remains low.

Animals↗
PubMed2006

The late effects of fetal growth patterns.

The immediate prenatal and postnatal consequences of reduced fetal growth have long been known. The longer term associations between reduced birth weight and adult disease risk are also now well established. Reduced fetal growth is usually detected late in gestation, and the assumption has been that this is the time when factors regulating fetal growth have their greatest effect. However, recent evidence suggests that both the growth trajectory of the fetus and its adaptive responses to the prenatal and postnatal environment may be determined in the period around the time of conception.

Animals↗
PubMed2001

Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep.

1. The purpose of this study was to examine the changes in circulating concentrations of insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-2 and insulin following asphyxia in utero. 2. Fetal sheep at 90-93 days gestation underwent either sham occlusion (n = 7) or asphyxia (n = 6) induced by complete umbilical cord occlusion for 30 min. Fetal blood samples were taken before occlusion and 4, 6, 24, 48 and 72 h post-occlusion. 3. During the early phase of recovery there was a substantial fall (80 %) in circulating plasma IGF-I concentrations by 6 h post-asphyxia (P < 0.001). This was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2. Insulin was significantly reduced at 4 h (P < 0.001) and glucose slightly elevated (P < 0.05), but insulin values returned to baseline by 6 h. Between 24 and 72 h of recovery, IGF-I gradually increased, IGFBP-1 returned to control values, and there was an increase in IGFBP-2 after 24 h (P < 0.05) and in IGF-II by 72 h (P < 0.05) after asphyxia. 4. These data demonstrate a differential effect of asphyxia on the IGF axis of the premature fetal sheep. A key finding was the large fall in circulating IGF-I, but not IGF-II, during the early phase of recovery. IGF-I bioavailability was, in part, regulated by IGFBP-1, but maximal changes in IGF-I and IGFBP-1 were independent of plasma insulin and glucose.5. The impact of this substantial change in circulating IGF-I on the fetus is unknown. It may facilitate metabolic requirements by promoting catabolism. Alternatively, as IGFs play a role in wound repair, the acute changes in IGF-I and IGFBP-1 may reflect transport of IGF-I from the circulatory pool to injured tissues to promote wound repair.

Animals↗
PubMed2001

Maternal undernutrition during the periconceptual period increases plasma taurine levels and insulin response to glucose but not arginine in the late gestational fetal sheep.

Maternal undernutrition throughout gestation impairs pancreatic function in the offspring. The influence of periconceptual maternal undernutrition on fetal insulin responses to secretogues in late gestation is unknown. Romney ewes were fed concentrates at 1-2% of body weight/d (UN) or 3-4% of body weight/d (N) from -61 d to +30 d from mating. From 30 d gestation all ewes were fed at 3-4% of body weight/d. At 119 d gestation singleton fetuses (UN; n = 12, N; n = 10) underwent intravenous glucose (1.5 g) and arginine (300 mg) challenge tests. Paired maternal and fetal blood samples were collected over 60 min. Fetal plasma insulin area under the curve (AUC) was larger in UN than in N fetuses during glucose challenge (4.5 +/- 0.6 vs. 2.9 +/- 0.5 nM, p < 0.05) but was not different during arginine challenge. Maternal and fetal plasma taurine concentrations were higher in UN than N (maternal; 110 +/- 11 vs. 75 +/- 8 microM, fetal; 99 +/- 13 vs. 56 +/- 5 microM, both p < 0.05). Maternal periconceptual undernutrition influences fetal insulin secretion without affecting fetal size. The larger plasma insulin responses in UN fetuses could reflect accelerated maturation of pancreatic beta cells or an alteration of other mechanisms regulating insulin secretion. The role of taurine in fetal pancreatic beta cell development requires further investigation.

Animals↗
PubMed2001

The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat.

GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms of these harmful effects of GH are unknown but have been, in part, ascribed to interactions between GH and the immune system. Because GH has pattern-dependent actions we have now compared the dose-related effects of continuous and intermittent GH treatment given with or without an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals monitored for a further 16 h. LPS administration alone led to neutrophilia and lymphopoenia, with increased plasma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 microg/kg per day) followed by LPS caused greater increases in plasma urea, cholesterol, triglyceride, sodium and magnesium, but lower plasma glucose and insulin levels, than treatment with LPS alone. In contrast, twice daily injections of GH did not enhance these effects of endotoxin. In conclusion, the effects of endotoxin on plasma electrolytes, lipids, urea, glucose and insulin are differentially affected by the pattern of GH administration in the rat.

Animals↗
PubMed1999

The maternal, fetal and postnatal somatotrophic axes in intrauterine growth retardation.

Both the maternal and fetal somatotrophic axes are closely linked to fetal substrate supply. Nutritional insults at critical stages of fetal development may lead to permanent reprogramming of the relationships between these factors. The consequences of reprogramming during fetal life may be harmful to metabolic, endocrine and cardiovascular homoeostatic mechanisms in postnatal life. The exact mechanisms that lead to reprogramming during fetal life need thorough investigation before effective strategies to deal with this problem can be devised.

Amniotic Fluid↗
PubMed1998

Fetal growth and placental function.

Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus via the placenta. However, this supply line can not be regarded as a linear relationship. Maternal undernutrition will not only reduce global nutrient availability but will also influence the maternal and fetal somatotrophic axis. Both endocrine systems react in a very similar way to limited substrate supply. The hormones of the fetal somatotrophic axis, and in particular insulin-like growth factor (IGF)-1, are important regulators of fetal growth. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. Placental function in turn, is heavily influenced by the maternal and fetal growth hormone (GH)-IGF-1 system. The placenta itself is also an active endocrine organ and it produces a large number of hormones including GH and IGF-1 as well their corresponding receptors. Thus the placenta can no longer be considered merely a passive conduit for fetal nutrition. Rather, it is actively involved in the integration of nutritional and endocrine signals from the maternal and fetal somatotrophic axes.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Fetal insulin-like growth factor (IGF)-I and IGF-II are regulated differently by glucose or insulin in the sheep fetus.

We investigated the effect of restoration of normoglycaemia or normoinsulinaemia in fetuses of starved ewes on plasma IGF-I and IGF-II concentrations. Paired maternal and fetal blood samples were taken during an initial 2-day control period, after 48 h of maternal starvation, during 24 h fetal infusion of glucose (n = 6) or insulin (n = 4) while maintaining maternal starvation and after 48 h maternal refeeding. After 48 h starvation maternal and fetal plasma IGF-I, insulin and blood glucose fell (maternal IGF-I 38.9 +/- 3.6 to 16.4 +/- 1.8 nM and fetal IGF-I 13.2 +/- 0.8 to 7.1 +/- 0.7 nM, both P < 0.05). Fetal plasma IGF-II also fell (147.8 +/- 9.1 to 112.2 +/- 3.8 nM, P < 0.05), but maternal plasma IGF-II rose (71.8 +/- 6.3 to 88.8 +/- 9.2 nM, P = 0.10). Fetal glucose replacement raised fetal plasma IGF-I (11.4 +/- 1.2 nM), IGF-II (149.7 +/- 6.5 nM), insulin and blood glucose to near control values (all P < 0.05). Fetal insulin replacement raised fetal plasma IGF-I (9.0 +/- 0.6 nM) and insulin (all P < 0.05) while IGF-II (105.2 +/- 8.4 nM) and blood glucose remained depressed. Neither fetal infusion had any significant effect on maternal plasma IGF-I (13.1 +/- 1.6 nM), IGF-II (77.5 +/- 8.7 nM), insulin or blood glucose. After 48 h maternal refeeding fetal IGF-I (12.4 +/- 0.4 nM), fetal IGF-II (158.4 +/- 8.9 nM), maternal IGF-II (67.1 +/- 3.0 nM), maternal and fetal insulin and glucose had returned to near control values in both groups. Maternal IGF-I remained below control values (24.7 +/- 2.5 nM, P < 0.05). The data suggest that fetal IGF-I and IGF-II are independently regulated in the fetal circulation. While glucose plays an important role in the regulation of both IGF-I and IGF-II, the influence of glucose on fetal IGF-I is likely to be mediated by insulin, whereas for IGF-II the effect of glucose is insulin-independent.

Animals↗
PubMed1996

Suppression of immune response in lambs during treatment with the beta-adrenergic agonist clenbuterol.

The effect of the beta-adrenergic agonist clenbuterol on immune function was examined in sheep. Twenty ewe lambs were housed indoors, with food and water available on an ad libitum basis, and immunized against somatostatin (SRIF) using a SRIF-ovalbumin conjugate. Ten of the lambs were also treated with clenbuterol (400 micrograms/kg) each day; 10 controls were not treated. After 5 wk of treatment (with booster injections of the SRIF conjugate each fortnight), the lambs were bled and then slaughtered for carcass composition. The lambs that received immunization alone produced significant antibody titers against SRIF, whereas 9 of the 10 clenbuterol-treated lambs produced no significant, specific antibody response. There was no effect of clenbuterol treatment on liver, thymus, spleen, kidney, kidney fat, or biceps femoris weight compared with those lambs that were only immunized. These results indicate that treatment with clenbuterol may inhibit humoral antibody response to infection.

Adrenergic beta-Agonists↗
PubMed1995

The effects of ovine placental lactogen infusion on metabolites, insulin-like growth factors and binding proteins in the fetal sheep.

It has been suggested, but not shown, that in the fetus placental lactogen (PL) may affect the regulation of the IGFs and fetal metabolism. To examine the effects of PL on the circulating concentrations of the IGFs, IGF-binding proteins (IGFBPs), glucose, free fatty acids (FFAs) and amino nitrogen (AN), we infused late gestation sheep fetuses with recombinant ovine PL (roPL). Five chronically-catheterised sheep fetuses were infused intravenously with three 24 h infusions of saline, roPL (100 micrograms bolus then 500 micrograms over 24 h) and then saline again. Fetal roPL infusion increased plasma oPL from 0.4 +/- 0.1 to 3.3 +/- 0.5 nM (mean +/- S.E.M.; P < 0.05; factorial analysis of variance and Scheffé's test). Fetal plasma IGF-I, IGF-II, insulin, FFAs and blood glucose were unaffected by the roPL infusion. Fetal plasma IGFBP-3, as measured by Western ligand blotting, decreased by 30% during fetal roPL infusion while other fetal plasma IGFBPs were unaffected. Fetal roPL infusion decreased fetal blood AN from 7.3 +/- 0.5 to 6.6 +/- 0.2 mM (P < 0.05). Maternal plasma IGF-I, IGF-II, IGFBPs, insulin, FFAs, blood glucose and AN were unaffected by the fetal roPL infusion. Saline infusion had no effect on any parameter. The data suggest that PL is not a significant determinant of plasma IGFs in the late gestation sheep fetus although there may be an indirect effect via alterations in levels of IGFBP-3. The effect of fetal roPL infusion on fetal blood AN concentrations may suggest some role for PL in the regulation of fetal amino acid metabolism.

Amino Acids↗
PubMed1994

Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin.

We have reported previously that levels of insulin-like growth factor I (IGF-I) and IGF-II in fetal sheep plasma decrease with maternal starvation and increase following an infusion of glucose to the starved fetus, while a fetal infusion of insulin elevates UGF-I alone. We now report the changes in the circulating IGF-II/M6P receptor and plasma IGF binding proteins (IGFBPs), as measured by western blotting and ligand blotting, respectively, in fetus and mother during this study. In fetal plasma, the circulating IGF-II/mannose-6-phosphate (M6P) receptor, IGFBP-3 and IGFBP-4 were reduced during starvation. While circulating IGF-II/M6P receptor and IGFBP-4 levels were increased following the fetal insulin or glucose infusion, IGFBP-3 was unchanged and increased only after 48 h of maternal refeeding. Both IGFBP-1 and IGFBP-2 increased with starvation but while IGFBP-1 levels returned to control values following both insulin and glucose infusion, levels of IGFBP-2 were not reduced significantly by either infusion or by refeeding. In maternal plasma, levels of IGFBP-3 and IGFBP-4 decreased while IGFBP-1 and IGFBP-2 increased after 48 h of starvation. Levels of each IGFBP were unaltered following the fetal infusions but returned to values obtained during the control period after refeeding. These data show that each of the IGF carrier proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1, or chronically, as for IGFBP-3. This suggests that the circulating IGF-II/M6P receptor and the IGFBP's may modulate IGF activity in the fetus during different nutritional states.

Animals↗
PubMed1993

Glucose but not a mixed amino acid infusion regulates plasma insulin-like growth factor-I concentrations in fetal sheep.

The influence of fetal glucose and amino acid supply on the regulation of fetal plasma IGF-I levels was investigated in fetuses from starved ewes. Paired maternal and fetal blood samples were taken during an initial 2-d control period, after 48 h of maternal starvation, during a 24-h fetal infusion of glucose (n = 6) or an amino acid mixture (Synthamin 17, n = 5) with continued starvation, and after 48 h of maternal refeeding. After 48 h of starvation, maternal and fetal plasma IGF-I, insulin, and blood glucose fell significantly in both groups compared with control values (IGF-I for glucose group: maternal, -18.53 +/- 6.60; fetal, -5.23 +/- 1.81 nmol/L; amino acid group: maternal, -18.2 +/- 6.97, fetal, -5.12 +/- 1.61 nmol/L; both p < 0.05). Fetal glucose but not mixed amino acid infusion raised fetal plasma IGF-I, insulin, and blood glucose to near control values (glucose group fetal IGF-I, -1.77 +/- 1.98; amino acid group, -5.93 +/- 2.22 nmol/L; both p < 0.05). Maternal plasma IGF-I remained depressed during glucose infusion (-16.33 +/- 8.32 nmol/L), but continued to fall in the amino acid group (-21.41 +/- 8.20 nmol/L, p < 0.05). After 48 h of maternal refeeding, all values had returned to near control values for both groups (glucose group IGF-I: maternal, -5.2 +/- 3.86; fetal, 0.01 +/- 2.2; nmol/L; amino acid group: maternal, -11.66 +/- 3.2; fetal, -0.70 +/- 2.61 nmol/L). We conclude that in the ovine fetus glucose may have a more important role than amino acids in the regulation of fetal plasma IGF-I.

Amino Acids↗
PubMed1992

The nutritional regulation of circulating placental lactogen in fetal sheep.

Maternal and fetal plasma ovine placental lactogen (oPL), insulin, and IGF-I levels were measured in response to the starvation and refeeding of pregnant sheep on two defined planes of nutrition. Chronically catheterized pregnant ewes were placed on either a high plane (n = 5) or low plane (n = 5) of nutrition at least 1 wk before the experiment. At 125 to 135 d gestation, the ewes were starved for 72 h and then an i.v. infusion of 10% glucose was administered over 4 h, followed by refeeding at the designated nutritional plane. Plasma oPL levels of fetuses whose mothers had been on a high plane of nutrition were significantly higher during starvation (p less than 0.05) than those of fetuses whose mothers had been on a low plane (high + 0.54 +/- 0.17 and low -0.02 +/- 0.17 nmol/L from mean control levels). Intravenous glucose infusion to the ewes at the end of starvation caused a marked rise in fetal plasma oPL levels in both groups (increments of 2.61 +/- 1.4 nmol/L in the high group and 2.81 +/- 1.16 nmol/L in the low group). Maternal oPL levels did not differ significantly between the two nutritional groups during starvation and did not change during glucose infusion. Fetal and maternal plasma IGF-I levels both fell during starvation. Maternal IGF-I levels fell faster in the high group (-17.9 +/- 4.5 at 24 h versus -4.7 +/- 7.2 nmol/L in the low group), but the groups were not different at the end of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1992

Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma.

Well-fed castrated male sheep (N = 3) and 125 days gestation pregnant ewes (N = 6) with chronically catheterized fetuses were fasted for 72 h. Insulin-like growth factor-binding protein (IGFBP) levels in fed and starved fetal, maternal and castrated male sheep plasma were measured using ligand blot analysis. IGFBPs in adult and fetal sheep differed in distribution both before and after 72 h starvation. IGFBP-3 was the major postnatal binding protein, while in the fetus IGFBP-2, IGFBP-3 and the circulating IGF type 2 receptor fragment each contributed 25-30% of total IGF binding capacity. After starvation, total IGF binding capacity and IGFBP-3 fell in plasma of maternal and castrated male sheep (p less than 0.05). Total IGF binding capacity rose with starvation in fetal plasma (p less than 0.05) as a result of an increase in IGFBP-1 (p less than 0.01) and IGFBP-2 (p less than 0.05). The different nutritional control of the IGFBPs in the fetus and the adult may reflect ontogenic differences in the regulation and function of circulating IGFs and their binding proteins.

Aging↗
PubMed1990

The effect of maternal starvation on plasma insulin-like growth factor I concentrations in the late gestation ovine fetus.

In view of the suggested relationship between substrate availability, fetal growth and circulating fetal IGF-I concentrations, we investigated the effect of maternal starvation on plasma IGF-I levels in the late gestation ovine fetus. Ten fetuses aged 125-130 d gestation were sampled daily from indwelling arterial catheters. Ewes were starved for 72 h. Starvation was terminated with an intravenous infusion of 10% glucose to the ewe. Food was then replaced 4 h later. Fetal IGF-I concentrations fell from 176.1 +/- 15.2 ng/mL before starvation to 124.5 +/- 10.3 ng/mL after 72 h starvation (p less than 0.05, n = 10). The fall in IGF-I concentrations was reversed by 4 h of maternal glucose infusion. In five fetuses, where samples were obtained 24 h after terminating the starvation, fetal IGF-I concentrations were comparable to those seen before starvation (180.0 +/- 37.7 ng/mL). This study demonstrates that acute maternal starvation causes a reversible decrease in fetal plasma IGF-I levels. These studies suggest that nutrient and in particular glucose availability is a significant determinant of fetal IGF-I secretion and support the hypothesis that IGF-I may play a role in the regulation of fetal growth.

Animals↗
PubMed1989

A rapid and convenient assay for counting cells cultured in microwell plates: application for assessment of growth factors.

There is currently much interest in the role of mediators that regulate cell proliferation. Methods to assay proliferative effects of such mediators usually involve cell counting techniques, which are tedious to perform, or methods based on uptake of radiolabelled thymidine, which may be prone to errors caused by precursor pool artefacts. We describe here an assay for estimating the number of adherent cells present in a microculture and its application to the study of growth factors. The assay depends on the binding of Methylene Blue to the fixed monolayer at pH 8.5 and, after washing the monolayer, release of dye by lowering pH. The use of an elution solvent containing acidified ethanol ensures a linear correlation between absorbance of the dye and cell number, and enables the assay to be carried out in 96-well plates measuring absorbance with an automated vertical light-path microplate photometer. The assay is rapid, highly reproducible and easy to perform, making it ideal for screening large numbers of samples. It was shown to be applicable to a number of foetal and adult cell lines derived from man and experimental animals. It was also demonstrated to be useful for assaying purified growth factors and detecting growth promoting activity in cell and tissue extracts.

Animals↗
PubMed1986

Collagen metabolism during right ventricular hypertrophy following induced lung injury.

Collagen synthesis and degradation rates were estimated in ventricles of normal rabbits and in those with right ventricular hypertrophy resulting from bleomycin-induced lung injury. Synthesis rates were estimated from the radioactivity in tissue [14C]hydroxyproline following a single intravenous injection of [14C]proline with a "flooding" dose of unlabeled proline (Biochem. J. 206: 535-544, 1982). The rate in the left ventricle was 5.8 +/- 1.0 compared with 2.9 +/- 0.4%/day in the right (P less than 0.02). Degradation rates, based on [14C]hydroxyproline levels in the tissue-free pool, indicated that in both normal ventricles about one-third of newly produced collagen was degraded rapidly following its synthesis. Six days after bleomycin, right ventricular collagen content fell by 35%, associated with a marked increase in tissue-free hydroxyproline levels. After 14 days the right ventricular weight and collagen content had increased by 49.4 +/- 3.7% (P less than 0.001) and 31.7 +/- 4.4% (P less than 0.05), respectively, and collagen synthesis rates increased to 9.7 +/- 1.8%/day (P less than 0.001). It is concluded that collagen is synthesized and degraded quite rapidly in normal heart tissue but that fractional rates differ between ventricles. The evidence also suggests that increased collagen synthesis and breakdown of mature collagen occurs as the connective tissue matrix is remodeled during adaptive cardiac growth.

Animals↗