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Biomedical subjects

G S Spencer

Publications and source records attributed to G S Spencer.

At least 19 recordsLinked to original sources
PubMed1999

The regulation of GH-dependent hormones and enzymes after feed restriction in dwarf and control chickens.

The principal objective of this study was to examine the GH-dependency of IGF-I and IGF-II changes in the chicken. To this end, the regulation of GH-dependent hormones and enzymes were studied in undernourished normal and dwarf chickens. The dwarf chickens examined exhibit a Laron-type dwarfism and have been shown to be GH receptor deficient. Thus, they provide an interesting model to determine the GH-dependency of IGF-I and IGF-II changes. Short (1 day) and long-term (7 days) feed restriction was imposed on growing normal and dwarf chickens to follow the subsequent endocrine changes. Since short-term feed restriction of dwarf chickens resulted in decreased plasma IGF-I, it appears that this is not a GH-dependent effect. However, with longer term undernutrition, IGF-I was not decreased in dwarf chickens. So, after a longer restriction period, the regulation of these factors appears to become more GH-dependent. IGF-II was not depressed at all by feed restriction in the dwarf chicken, suggesting a degree of GH-dependency.

Animals↗
PubMed1997

Correctly accounting for radiofrequency spillover in saturation transfer experiments: application to measurement of the creatine kinase reaction rate in human forearm muscle.

Measurements based on transfer of magnetization have been widely used to calculate reaction rates in systems with slow chemical exchange. In these experiments, correction for direct irradiation of the observed resonance is in general accomplished by replacing the equilibrium magnetization in the Bloch equations by a magnetization obtained in an experiment in which a low power radio-frequency (RF) pulse is placed contralaterally, that is, at an equal distance from the observed resonance as the saturated one but on the opposite side. However, the magnetization observed during contralateral irradiation is affected not only by direct irradiation but also by chemical exchange. We demonstrate here that including this effect leads to a substantial improvement in the accuracy of reaction rate determination in steady-state saturation transfer experiments and, if incomplete saturation is present, also in transient saturation transfer experiments. In steady-state saturation transfer experiments performed in vivo at 1.9 T, correct interpretation of the contralateral saturation transfer experiment resulted in a correction of the creatine kinase reaction rate by approximately 11% on average.

Adenosine Triphosphate↗
PubMed1997

Basal secretion of growth hormone in sheep is not influenced by GH feedback.

Autoregulation of GH secretion in sheep was examined by intravenous and intracerebroventricular (i.c.v.) administration of human and bovine GH. Intravenous administration of hGH at either 2 mg or 10 mg per sheep failed to alter radioimmunoassayable plasma ovine GH concentrations or plasma somatostatin. Human GH also failed to alter plasma oGH when given at a dose of 50 micrograms i.c.v. Bovine GH (at 50 micrograms or 500 micrograms) i.c.v. did not affect basal plasma oGH or somatostatin, nor did pretreatment with 50 micrograms bGH significantly alter GH response to clonidine stimulation, although the change in plasma GH with stimulation was only half that of controls. These data do not support a major autoregulatory effect on GH secretion in the sheep.

Animals↗
PubMed1997

Physiological inhibition of growth hormone secretion by both insulin-like growth factors-I and -II in chickens.

1. The role of both insulin-like growth factors (IGF)-I and -II in regulation of growth hormone (GH) secretion in chickens was examined. Seven-week-old male broiler chickens were injected intravenously (i.v.) with recombinant human IGF-I or IGF-II or specific anti-IGF-I or IGF-II immunoglobulins. Blood samples were taken before treatment and at 15 min intervals afterwards for 1 h. Controls received saline i.v. 2. Both IGF-I and IGF-II administration resulted in a rapid, significant decrease in plasma GH concentrations, but the concentrations of both triiodothyronine and thyroxine remained unchanged. 3. Immunisation against both IGF-I and IGF-II produced a significant elevation in plasma GH. 4. These data show that both IGFs can regulate GH concentrations in birds. Furthermore, the immunoneutralisation data suggest that these hormones have a physiological role in the regulation of GH secretion.

Animals↗
PubMed1996

Evidence for suppression of immune function by insulin-like growth factor-1 in dwarf rats in vivo.

These studies were undertaken to investigate the effects of increasing or decreasing IGF-1 levels on aspects of immune function in rats. Female dwarf rats were treated with recombinant human IGF-1 or with a potent sheep anti-IGF-serum. Body weight, thymus weight and spleen weight increased with IGF-1 treatment (p < 0.001), while there was no effect of anti-IGF-1 treatment when compared with the appropriate normal sheep serum (NSS) treated controls. IGF-1 treatment significantly decreased WBC and RBC counts, but increased the ratio of CD4+:CD8+ T-cells. Anti-IGF-1 serum had no effect on these parameters compared with NSS. However anti-IGF-1 was associated with increased T-cell numbers, decreased natural killer cells, and enhancement of the animals' ability to produce specific IgG in response to injection of keyhole limpet haemocyanin (KLH). These results indicate that IGF-1 may suppress immune function although increasing the size of immune organs such as spleen.

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↗
PubMed1996

Effect of recombinant human insulin-like growth factor-II on weight gain and body composition of broiler chickens.

Osmotic minipumps containing either saline or recombinant human insulin-like growth factor-II (IGF-II) were implanted into 4-wk-old female broiler chickens such that the treated chickens received 0.5 mg IGF-II/kg body weight per d. At the end of the trial, no differences in body weight gain or bone length were detected between the treated and control groups. Similarly, there were no differences between the two treatments with respect to heart, spleen, liver, or bursa of Fabricius weight. The relative weight of the abdominal fat pads was greater (P < 0.05) in the birds treated with IGF-II than in the controls, whereas the weight of breast muscle was reduced (P = 0.06) in the birds treated with IGF-II. There was no effect of IGF-II treatment on feed intake or feed conversion efficiency. Plasma growth hormone (GH) levels were acutely depressed by 15 min after IGF-II administration; and also after 2 wk of IGF-II treatment. Plasma triiodothyronine (T3) concentrations were significantly depressed by IGF-II treatment. These results suggest that IGF-II may not stimulate growth in chickens, but can act as a nutrient partitioning agent, either directly or indirectly through altering plasma GH or T3 concentrations.

Adipose Tissue↗
PubMed1995

Growth hormone alters lymphocyte sub-populations and antibody production in dwarf rats in vivo.

Female dwarf rats at different ages were treated with recombinant porcine GH or with a potent sheep anti-rat GH serum. Body weight and spleen weight increased with GH and decreased with anti-GH treatment (p < 0.001). Neither GH nor anti-GH treatment resulted in a change in circulating WBCs, but GH decreased, while anti-GH increased, RBC counts (p < 0.001). Similarly, GH treatment tended to decrease the ratio of CD4+:CD8+ T-cells while anti-GH increased (p < 0.05) the ratio. Anti-GH treatment also enhanced the animals' ability to produce specific IgG in response to KLH injection. These results indicate that GH may have a physiological role in suppressing humoral immune function but may enhance cell-mediated immunity.

Animals↗
PubMed1995

Passive immunization of insulin-like growth factor (IGF)-1 and of IGF-1 and IGF-2 in chickens.

The effects of passive immunization against IGF-1 either alone, or together with immunization against IGF-2, on growth and metabolism were examined in chickens. Immunization against IGF-1 alone had no effect upon any aspect of growth, carcass composition, efficiency of energy utilization or hormone concentrations studied. Immunization against both IGF-1 and IGF-2 together resulted in a lighter final body weight (P < 0.05) compared with controls. Immunization against both IGFs together decreased abdominal fat content (P < 0.05) and resulted in a heavier mean spleen weight (P < 0.01). The joint immunization was also associated with elevated plasma T3 concentrations. These data may indicate a role for IGF-2, but not for IGF-1, in fat metabolism in chickens.

Adipose Tissue↗
PubMed1994

Neuroendocrine regulation of growth hormone secretion in sheep. VII. Effects of GABA.

The effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) administration of gamma aminobutyric acid (GABA) on plasma growth hormone (GH) concentrations have been examined in sheep. Intravenous administration of GABA resulted in a rapid, significant (P < 0.001) increase in plasma GH. Administration of 10 mg of GABA i.c.v. produced a significant (P < 0.001) increase in GH release. By contrast, 100 mg given i.c.v. was inhibitory and resulted in a decrease (P < 0.05) in plasma GH levels. Concurrent administration of somatostatin (0.5 microgram/min i.v. over 1 h) did not alter the plasma GH response to 10 mg GABA given i.c.v. These data are consistent with the concept of dual sites of action for GABA in regulating GH release in sheep, but the exact mechanism through which this effect is mediated remains unclear.

Animals↗
PubMed1994

Neuroendocrine regulation of growth hormone secretion in sheep. VI. Intracerebroventricular administration of galanin.

The effects of intracerebroventricular (i.c.v.) administration of galanin on plasma growth hormone (GH) concentrations and its possible mechanism of action have been examined in sheep. Galanin administration icv resulted in a dose-dependent increase in plasma GH concentrations (p < 0.01). Concurrent administration of somatostatin (0.5 microgram kg-1 i.v. over 30 min) caused a delay in the GH response to galanin, but did not inhibit the GH release. These data show that galanin can stimulate GH release in sheep, but the mechanism through which this effect is mediated remains unclear.

Animals↗
PubMed1994

Alteration of maternal growth hormone levels during pregnancy influences both fetal and postnatal growth in rats.

To study the effects of exogenous growth hormone (GH) administration to the mother on fetal growth, dwarf rats with an isolated GH deficiency were given daily s.c. injections of GH throughout pregnancy. Fetuses were heavier in GH-treated mothers (p < 0.001), and pups from GH-treated mothers continued to grow faster (p < 0.001) than pups from control mothers throughout the postnatal growth period through to weaning. In normal Wistar rats, administration of a potent antiserum to somatostatin to pregnant rats increased the mean birth weight of the offspring (p < 0.01). Administration of GH to the mothers also significantly increased birth weight (p < 0.05), but administration of antiserum to rat GH resulted in a significant retardation of both fetal and placental growth (p < 0.001). These data suggest that maternal GH status is significantly involved in the growth of the fetal rat.

Animals↗
PubMed1994

Glycosaminoglycan binding characteristics of the insulin-like growth factor-binding proteins.

Interactions between the IGF-binding proteins (IGFBPs) and glycosaminoglycans (GAGs) such as heparin may be involved in the regulatory control of IGF exerted by the IGFBPs at the level of the extracellular matrix and capillary endothelium, although the precise mechanisms of this remain uncertain. We have searched primary sequences of human, rat and bovine IGFBPs-1 to -6 for putative GAG-binding consensus sequences (XBBXBX and XBBBXXBX, where B represents any basic amino acid and X is undefined). At least one such sequence was identified in each IGFBP examined except human and rat IGFBP-4 and rat IGFBP-6, with IGFBP-5 containing three GAG-binding consensus sequences. Additionally, the bovine IGF type II receptor was found to contain two such sequences in the intracellular region. Affinity of the IGFBP preparations for heparin was examined experimentally by affinity chromatography using pooled fractions of fetal and adult ovine plasma obtained by size exclusion chromatography. Pooled fractions of 150 kDa (containing IGFBP-3 alone by IGF ligand blot analysis) and 40-50 kDa (containing IGFBPs-3 and -2, together with proteins of 29, 24 and 25-28 kDa which may include IGFBP-4 and IGFBPs-1, -5 and -6) were found to bind strongly to the matrix necessitating high salt concentrations for their elution; however, in contrast, a > 200 kDa fraction containing the soluble form of the type II receptor failed to bind. Recombinant human non-glycosylated IGFBP-3 also bound strongly to the affinity adsorbent. No evidence of dissociation of bound IGF from binding protein complexes by association with the matrix was obtained from this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Hormone and metabolite changes with stress in stress-susceptible pietrain pigs.

Pigs of the stress-susceptible Pietrain breed, weighing about 60 kg liveweight, were fitted with indwelling jugular vein catheters which were exteriorized between the shoulders to allow stress-free blood sampling. After surgery, the animals were placed in metabolism crates and allowed at least seven days to recover and to become accustomed to handling, and to their environment, before experimentation. On the day of study, the pigs were subjected to a stimulated loading stress. Blood samples were taken both before, and a number of times after, the stimulated loading procedure. Plasma levels of: glucose, insulin, lactate, and thyroxine rose rapidly to peak levels at 10 min after simulated loading. Cortisol and triiodothyronine rose to peak levels 15-20 min after the stressor was applied, while free fatty acid levels were initially depressed, but later showed a rise at 120 min. From these results it seems that plasma cortisol, thyroid hormones and lactate concentrations may prove to be useful indicators of stress, either individually or in combination.

Animals↗
PubMed1993

Evidence of a role for growth hormone, but not for insulin-like growth factors-I or -II in the growth of the neonatal rat.

Neonatal rats were injected with antiserum raised against either insulin-like growth factor (IGF)-I, IGF-II, rat growth hormone (rGH) or somatostatin (SRIF) on each of days 2-5 of life: controls received normal sheep immunoglobulin. Plasma levels of rGH and IGF-I were measured by radioimmunoassay and growth rates recorded. Neonatal administration of anti-rGH resulted in the suppression of plasma IGF-I levels at day 21 and of body weight gain compared with control animals from day 5 of age; relative growth velocity continued to diverge in the absence of any further treatment. Immunoneutralization of IGF-I or of IGF-II had no effect on growth rates of rats at any time during the experiment and had no effect upon plasma rGH concentrations at day 21. However, at day 7, plasma rGH was lower in anti-IGF-I-treated rats than in controls; in contrast, plasma rGH in anti-IGF-II-treated animals at day 7 was higher than in controls. Plasma levels of IGF-I at 49 days of age were similar regardless of the neonatal immunization treatment received. Anti-SRIF treatment of neonatal rats was associated with elevated rGH levels, but no significant stimulation of growth. These results indicated that growth hormone, but not circulating IGF-I or IGF-II are essential for normal growth in the neonatal rat.

Animals↗
PubMed1993

Regulation of plasma and tissue levels of insulin-like growth factor-I by nutrition and treatment with growth hormone in sheep.

Tissue and plasma levels of insulin-like growth factor-I (IGF-I), and relative levels of liver IGF-I RNA, were measured in 6-month-old ewe lambs which were well fed (n = 10) or starved (n = 10) for 5 days. Half of each nutrition group was given daily (09.00 h) injections of human GH (hGH; 0.15 mg/kg body weight per day). Blood was sampled daily from 09.00 to 12.00 h at 15-min intervals through jugular vein catheters and the lambs were slaughtered 24 h after the fifth injection of hGH. Tissue and plasma IGF-I was extracted using an acid-ethanol-cryo-precipitation technique and estimated by radioimmunoassay. Tissue IGF-I was corrected for retained plasma IGF-I using tissue and blood hemoglobin levels. Liver IGF-I RNA levels were monitored by in-situ hybridization. Plasma IGF-I (nmol/l) was higher in both the fed group and the fed group given GH treatment. Tissue IGF-I from kidneys (nmol/kg) was also higher (P < 0.001) in the fed group. There was no significant difference in IGF-I concentrations in the muscle biceps femoris or liver between fed and starved lambs. Although GH treatment did not increase IGF-I levels in tissues significantly, IGF-I RNA levels in liver were increased (P = 0.02) in both fed and starved animals. The relative liver IGF-I RNA levels positively correlated with their corresponding tissue IGF-I levels in the fed group and the fed group given GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1993

Receptors for insulin-like growth factor-II in the growing tip of the deer antler.

Insulin-like growth factor-II (IGF-II) binding in the growing tip of the deer antler was examined using autoradiographical studies, radioreceptor assays and affinity cross-linking studies. Antler tips from red deer stags were removed 60 days after the commencement of growth, and cryogenically cut into sections. Sections were incubated with radiolabelled IGF-II, with or without an excess of competing unlabelled IGF-II and analysed autoradiographically. Radiolabelled IGF-II showed high specific binding in the reserve mesenchyme and perichondrium zones, which are tissues undergoing rapid differentiation and cell division in the antler. Binding to all other structural zones was low and significantly (P < 0.001) less than binding to the reserve mesenchyme/perichondrium zones. Radioreceptor assays on antler microsomal membrane preparations revealed that the IGF-II binding was to a relatively homogeneous receptor population (Kd = 1.3 x 10(-10) mol/l) with characteristics that were not entirely consistent with those normally attributed to the type 2 IGF receptor. Tracer binding was partly displaceable by IGF-I and insulin at concentrations above 10 nmol/l. However, affinity cross-linking studies revealed a single band migrating at 220 kDa under non-reducing conditions, indicative of the type 2 IGF receptor. These results indicate that, in antler tip tissues, IGF-II binds to sites which have different binding patterns and properties from receptors binding IGF-I. This may have functional significance as it appears that, whilst IGF-I has a role in matrix development of cartilage, IGF-II may have a role in the most rapidly differentiating and proliferating tissues of the antler.

Animals↗