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Biomedical subjects

C G Prosser

Publications and source records attributed to C G Prosser.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-like growth factor binding proteins of equine serum.

Ligand blotting analysis of serum from the horse using radiolabelled IGF-I revealed a protein at 96 kDa which was not present in serum from goat, cow, sheep, deer or donkey. These latter species all displayed five labelled bands in the range 24 to 41 kDa. Conversely, these were only weakly labelled in serum from the horse. Size exclusion chromatography of horse serum pre-incubated with radiolabelled IGF-I revealed reduced binding in the 130-kDa peak compared with goat plasma, and ligand blotting analysis indicated the 96-kDa protein was present in this peak. The 96-kDa protein from horse serum binds IGF-I and IGF-II specifically and appears to be unique to this species. The nature of this protein is at present unknown.

Animals↗
PubMed1992

Secretion of insulin-like growth factor II into milk.

125I-labeled insulin-like growth factor II (IGF-II) was infused directly into the pudic artery supplying one gland of lactating goats (n = 4). Maximum specific activity for [125I]IGF-II transferred into milk from the infused gland was reached 60 min after that in plasma and was 2.5 fold greater than in milk from the non-infused gland. Inclusion of either 67.5 nmoles unlabeled IGF-II or IGF-I had no influence on the amount or pattern of secretion of [125I]IGF-II into milk from either gland. While the temporal pattern of secretion of [125I]IGF-II into milk was consistent with a transcellular mechanism of transfer, the lack of competition by unlabeled IGF-II or IGF-I suggests a non-specific mechanism is operable, which contrasts to secretion of IGF-I.

Animals↗
PubMed1992

Effect of colostrum intake on alpha-lactalbumin concentrations in serum of calves.

Seven Friesian calves were fed colostrum for four days beginning within 24 hours of birth, and milk thereafter. The concentration of alpha-lactalbumin in serum was measured by specific radioimmunoassay and compared to IgG assayed by electroimmunodiffusion. Serum concentrations of alpha-lactalbumin peaked at 387 +/- 85 ng ml-1 within eight hours of initial intake of colostrum, declining to 12 +/- 3 ng ml-1 by day 6. IgG rose steadily to 17 mg ml-1 by 48 hours of birth and remained relatively constant thereafter. The temporal pattern of alpha-lactalbumin in serum following colostrum intake confirms previous studies suggesting reduced absorption of colostral proteins between 24 and 36 hours. The presence of variable amounts of alpha-lactalbumin in serum even after 17 days, however, indicates limited transfer of milk-derived proteins across the gut at this time. The data further show that cessation of maximal gut transfer does not relate to molecular weight of transferred protein.

Animals↗
PubMed1992

Transfer of insulin-like growth factors I and II from plasma to lymph in young goats.

The plasma clearance of intravenously injected 125I-labelled insulin-like growth factor I (IGF-I, n = 13) and IGF-II (n = 12) and their transfer into lymph draining the foreleg of 3.5- to 8-week-old British Saanen goats was studied. Both peptides were initially distributed into a volume equivalent to the plasma volume, while the final distribution spaces for IGF-I and IGF-II were 90 +/- 9.8 and 125 +/- 12 ml/kg live weight respectively. There were two phases to the plasma clearance of both IGF-I and IGF-II, with the half-lives of both phases for IGF-I (9.6 +/- 0.9 and 287 +/- 23 min, first and second phase respectively) being significantly (P less than 0.001) longer than those of IGF-II (4.2 +/- 0.6 and 172 +/- 18 min, respectively). The radioactivity transferred into lymph originated from intact IGF-I and IGF-II as well as degraded products of these compounds, as assessed by precipitation with trichloroacetic acid and gel filtration. Levels of undegraded IGF-I in lymph were 50% greater than IGF-II. While more than 90% of either peptide was bound to specific IGF-binding proteins in plasma, in lymph 34 +/- 2% of IGF-I and 23 +/- 3% of IGF-II remained in the free form 60-80 min after injection. The plasma: lymph ratio for free IGF-I was 2:1 and for bound IGF-I, 8:1. The corresponding values for IGF-II were 3:2 and 8:1 respectively. These results provide direct experimental evidence for transfer of undegraded IGF-I and IGF-II from blood into lymph of the foreleg, consistent with the ability of these factors to act in an endocrine role in growing tissues. Differences between plasma clearance and transfer of IGF-II into lymph compared with IGF-I may be due to its greater cellular uptake and/or degradation in vivo.

Animals↗
PubMed1992

Effect of growth hormone treatment on the distribution of insulin-like growth factor-I between plasma and lymph of lactating sheep.

Plasma and mammary efferent lymph concentrations of insulin-like growth factor I (IGF-I) were determined in lactating ewes before and after treatment with GH (10 mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0.34 to 0.47 after GH treatment when the IGF-I content of plasma increased by 19.4 nmol/l (from 32.1 nmol/l) and lymph by 13.7 nmol/l (from 10.7 nmol/l). This increase in the relative content of IGF-I in lymph was associated with increased lymph content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by size exclusion chromatography. GH treatment increased the total binding capacity for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma and the 150 kDa pool in lymph but there was a proportionally greater increase in 50 kDa total binding in lymph relative to plasma. Further, GH treatment increased the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of the 150 kDa fraction, in both plasma and lymph. Ligand blot analysis of IGF-binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph. Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0.68 to 0.87. GH treatment of lactating ewes not only increased the IGF-I content of plasma but increased the apparent efficiency of transfer of IGF-I across capillary endothelium to mammary efferent lymph.

Animals↗
PubMed1992

Milking frequency alters the milk yield and mammary blood flow response to intra-mammary infusion of insulin-like growth factor-I in the goat.

The milk yield and mammary blood flow responses to close-arterial, intra-mammary infusion of IGF-I were investigated in five Saanen goats milked frequently or normally the day before. Animals were infused for 6 h with recombinant human IGF-I (1.3 nmol/min) and milked hourly following i.v. injection of oxytocin beginning 2 h before infusion and then every 2 h. On one occasion animals were milked five times (after i.v. injection of oxytocin) on the day before infusion and on the other they were milked twice, without oxytocin. The ratio of milk yield from the infused to that from non-infused gland increased by 17 +/- 4% (mean +/- S.E.M.) in goats milked twice the day before infusion and by 6 +/- 2% when the infusion was preceded by frequent milking. Maximal responses were obtained 4 h after the start of the infusion and differed significantly (P < 0.05), according to pretreatment milking. Blood flow through the infused gland rose in parallel to the milk yield response. At 5 h, when maximal levels were achieved, blood flow was 182 +/- 23% of the pre-infusion flow rate following twice-daily milking and 139 +/- 3% of the pre-infusion flow rate following more frequent milk removal. Thus, more frequent milk removal on the day before close-arterial infusion of IGF-I attenuated both the milk yield and mammary blood-flow response to the infusion of IGF-I.

Animals↗
PubMed1991

The galactopoietic effect of bovine growth hormone in goats is associated with increased concentrations of insulin-like growth factor-I in milk and mammary tissue.

Lactating goats exhibiting widely divergent responses to short-term (4 days) treatment with bovine GH (bGH) were retrospectively divided into two groups based on the magnitude of this response. There was no difference between groups in terms of the pretreatment milk yield, but by day 4 of treatment milk secretion had increased by 4.99 +/- 2.5 (S.E.M.) ml/h (P greater than 0.05 compared with pretreatment) for group 1 and 22.9 +/- 2.4 ml/h (P less than 0.001) for group 2. Plasma GH increased in both groups, but concentrations were significantly higher both before and during treatment in group 1 compared with group 2. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly during bGH treatment for both groups and there was no significant difference between the two until day 4 of treatment when levels of IGF-I in group 1 began to decline, whereas those from group 2 were maintained. Concentrations of IGF-I in milk from goats in group 1 were not significantly altered by GH administration, whereas those in goats in group 2 were increased by 40% (P less than 0.01 compared with pretreatment). Levels of IGF-I in mammary secretory tissue from four animals from group 1 were not altered by bGH (2.8 +/- 0.2 and 2.77 +/- 0.08 nmol/kg tissue before and after treatment respectively), but were significantly (P less than 0.05) increased in four animals from group 2 (2.80 +/- 0.2 and 9.9 +/- 1.1 nmol/kg tissue).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mechanism of secretion of plasma insulin-like growth factor-I into milk of lactating goats.

125I-Labelled insulin-like growth factor-I (IGF-I) was infused as the free form directly into the pudic artery supplying one gland of lactating goats (n = 6). The infusion was for 60 min and 0.4 +/- 0.09% (S.E.M.) of the infusate was secreted into milk from the infused gland during its first passage through that gland. A large proportion of the 125I-labelled IGF-I escaped into the systematic circulation and was secreted into milk of both glands. A total of 5.2 +/- 0.4% of infused radioactivity was recovered in milk from both glands from 0 to 720 min. Radioactivity consisted of trichloroacetic acid (TCA)-precipitable and -soluble counts which were shown by gel filtration to be authentic IGF-I and degraded products of the peptide. The amount and time course of TCA-soluble radioactivity in milk from both glands was similar, suggesting degradation of 125I-labelled IGF-I at extramammary sites. Maximum specific activity for 125I-labelled IGF-I in milk from the infused gland was reached 80-120 min after the start of infusion and was 2.5-fold greater than milk from the non-infused gland. The time course of appearance of 125I-labelled IGF-I in milk suggests that transfer was via the transcellular pathway and this was further supported by comparing the pattern of transfer of [14C]sucrose and [14C]amino acids. When excess unlabelled IGF-I was included in the infusate, specific activity in milk from the infused gland was reduced to that of the non-infused gland, indicating a competitive and saturable mechanism of secretion for 125I-labelled IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increase in milk secretion and mammary blood flow by intra-arterial infusion of insulin-like growth factor-I into the mammary gland of the goat.

The close-arterial infusion of free insulin-like growth factor-I (IGF-I; 1.1 nmol/min) for 6 h into the pudic artery supplying one mammary gland of lactating goats caused a 25 +/- 6% (mean +/- S.E.M., n = 6) increase in the rate of milk secretion of that gland. The increase in the rate of milk secretion in the adjacent noninfused gland (14 +/- 4%) was not significantly different from that observed during saline infusion (4 +/- 5%). Blood flow to the infused gland was increased from 378 +/- 26 ml/min 1 h before to 487 +/- 56 ml/min approximately 5 h after the start of the infusion of IGF-I, declining to 420 +/- 44 ml/min approximately 2 h after the end of the infusion. The total concentration of IGF-I (free and bound) in milk of the infused gland was significantly higher than that of the non-infused gland. The concentrations of IGF-I in carotid arterial plasma samples increased during IGF-I infusion from a mean value of 32 +/- 2 nmol/l before to a maximum of 49 +/- 3 nmol/l 5 h after the infusion commenced. Circulating concentrations of total IGF-I declined slowly after the infusion with an estimated half-life of 5 h. Infusion of saline alone did not alter mammary blood flow or the concentration of total IGF-I in milk or plasma. The results indicate that the infusion of free IGF-I into the mammary arterial supply enhances milk secretion and mammary blood flow in intact, conscious goats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Increased secretion of insulin-like growth factor I into milk of cows treated with recombinantly derived bovine growth hormone.

Six lactating, non-pregnant Jersey cows were given subcutaneous injections of recombinantly derived bovine growth hormone for 7 d. Milk yield was increased by 4.5 kg/d on d 7, compared with the average yield of 10.7 +/- 0.4 kg/d (mean +/- s.e.m.) for the 7 d preceding treatment. Concentrations of insulin-like growth factor I (IGF-I) in the milk increased from 0.44 +/- 0.04 nmol/l (mean +/- s.e.m.) during the 7 d preceding treatment to 1.6 +/- 0.2 nmol/l on d 7 of treatment. Taking the increase in milk yield into account the total increase in the secretion of IGF-I into milk of one udder half was 6-fold. Plasma concentrations of total IGF-I rose from 15.5 +/- 1.3 nmol/l (mean +/- s.e.m.) on the day preceding treatment to 56.9 +/- 3.6 nmol/l (mean +/- s.e.m.) on d 7 of treatment. Mammary plasma flow increased from 1.6 +/- 0.09 to 2.2 +/- 0.06 l/min.udder half over the same time. Estimates of the amount of IGF-I that reached the mammary gland gave values of 24 and 116 nmol/min.udder half before and during treatment respectively. IGF-I in milk of treated cows was associated predominantly with proteins ranging from 40,000 to 150,000 mol.wt, but a significant proportion (19%) of the total IGF-I was present in the free unbound form. IGF-I crosslinking studies revealed the presence in milk of one specifically labelled band at 31,000 mol.wt.

Animals↗
PubMed1988

Mechanism of the decrease in hexose transport by mouse mammary epithelial cells caused by fasting.

The basal carrier-mediated uptake of 0.5 mM-3-O-methylglucose by mammary epithelial cells from lactating mice was calculated to be 227 +/- 9 pmol/min per microgram of DNA (mean +/- S.E.M., n = 11). Fasting the mice for 16 h overnight resulted in a decrease in this rate to 65 +/- 4 pmol/min per microgram of DNA (n = 10). Refeeding the fasted mouse for 3 h before isolation of the cells restored the transport activity to 230 +/- 12 pmol/min per microgram of DNA (n = 12). The Vmax. for equilibrium exchange entry of 3-O-methylglucose by intact cells was decreased from 6.6 +/- 0.4 to 0.9 +/- 0.2 nmol/min per microgram of DNA (mean +/- S.E.M., n = 3) by fasting. The number of D-glucose-inhibitable cytochalasin-B-binding sites in a plasma-membrane-enriched fraction of the cells was also decreased from 5.7 +/- 1.5 to 1.7 +/- 0.1 pmol/mg of membrane protein (mean +/- S.E.M., n = 3). Again, refeeding the fasted mouse for 3 h reversed both these effects. These results are consistent with a decrease in the number of functional glucose carriers in the plasma membrane of the mammary epithelial cells. Since the restoration of transporter activity after refeeding does not appear to require the synthesis of new protein, the effect of fasting probably involves not a loss of transporters, but a change in their orientation within the plasma membrane or a redistribution within the cell.

3-O-Methylglucose↗
PubMed1988

The insulin-like growth factor I content in human milk increases between early and full lactation.

The concentration of immunoreactive insulin-like growth factor I (IGF-I) in human mammary secretions, assayed after acid-ethanol extraction, was high [mean, 4.1 +/- 0.5 (+/- SE) nmol/L; n = 13] for several weeks prepartum. It then decreased during the first 3 days postpartum to 1.3 +/- 0.1 nmol/L (n = 28), in parallel with changes in epidermal growth factor (EGF) and protein concentrations. However, between the first and sixth weeks postpartum, the IGF-I concentration increased to 2.5 +/- 0.2 nmol/L (n = 18), while levels of EGF and protein decreased further. Given that the volume of milk produced increases during this period, the total IGF-I output rose by up to 4-fold, while EGF output remained constant. The increase in IGF-I and decrease in EGF in milk suggest that different regulatory mechanisms control the output of different growth factors by the mammary gland.

Epidermal Growth Factor↗
PubMed1988

From animal to molecule: aspects of the biology of insulin-like growth factors.

The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Comparison of the roles of insulin and insulin-like growth factor I in casein gene expression and in the development of alpha-lactalbumin and glucose transport activities in the mouse mammary epithelial cell.

The concentration-activity profiles for insulin and insulin-like growth factor I (IGF-I; in the presence of and insulin-like growth factor I (IGF-I; in the presence of hydrocortisone and PRL) have been compared in terms of the accumulation of beta-casein mRNA, total casein synthesis, and alpha-lactalbumin and basal carrier-mediated glucose transport activities in mammary epithelial cells from midpregnant mice. For the accumulation of the casein mRNA and the induction of casein synthesis and alpha-lactalbumin activity, the insulin ED50 is 1-2 ng/ml, while that for IGF-I is 10- to 20-fold greater. The effects of insulin and IGF-I are not additive in these instances. For the induction of basal carrier-mediated glucose transport, the insulin ED50 is 8 ng/ml, and that for IGF-I is 16 ng/ml. Either factor can induce transport activity up to the level present in the cells from 2-day lactating mice. In this instance the effects are additive; insulin and IGF-I together can induce the transport up to the 10-day lactating level.

3-O-Methylglucose↗
PubMed1986

Changes in the rate of carrier-mediated glucose transport by mouse mammary epithelial cells during ontogeny: hormone dependence delineated in vitro.

Epithelial cells were isolated from mammary glands of mice in various physiological states, and the rate of carrier-mediated glucose transport was determined with 3-O-methylglucose. The basal rate (in the absence of exogenous insulin) increases about 40-fold as the animal of origin progresses from the virgin to the midlactating state and declines precipitously during involution. Insulin does not acutely stimulate carrier-mediated transport by cells isolated from virgin or lactating mice and evokes only about a 50% enhancement of this transport rate in the cells derived from pregnant and early postlactational animals. However, culture of mammary explants from pregnant mice in the presence of insulin, cortisol, and PRL before isolation of the epithelial cells results in a 400% increase in the basal rate of carrier-mediated glucose transport in the absence of exogenous hormones; this effect requires 3 days of incubation. The enhanced rate is equivalent to that in cells freshly isolated from animals in early lactation. Insulin-like growth factor I can mimic the chronic effect of insulin, but multiplication-stimulating activity, epidermal growth factor, and 20% fetal calf serum do not supplant insulin in this system. The maximum velocity, but not the Km, of 3-O-methylglucose transport is markedly increased during ontogeny; this is compatible with an increase in the number of functional transporters during development. The results suggest that insulin and/or insulin like growth factor I are implicated in development of the high basal rate of carrier-mediated glucose transport in mammary cells from lactating mice.

3-O-Methylglucose↗
PubMed1984

Mammary gland function during gradual weaning and early gestation in women.

Daily changes in the composition of the milk of two lactating women were recorded from the time of the last menstrual period prior to conception throughout the first two months of gestation. The changes in the composition of the milk from these women were compared to the daily changes in the milk composition of two women during the period of gradual weaning. In the weaning subjects the concentration of sodium and total protein had increased 14- and 1.6-fold, respectively, by the end of the study. The concentrations of potassium, glucose and lactose decreased 1.3-, 149- and 3.6-fold, respectively, from before weaning commenced to the end of the study. These changes were closely correlated to the decrease in the suckling frequency of the infant. The concentration of sodium and total protein in the milk from the unsuckled breast of two women was 11- and 2.8-fold higher than in the milk from the normally suckled breast of the same woman. The concentrations of potassium, glucose and lactose were 1.1-, 70- and 1.9-fold lower, emphasizing the necessity of a regular suckling pattern on the maintenance of lactation. The concentrations of sodium and total protein similarly increased during pregnancy, being 8- and 3.8-fold higher by the second month of gestation. The concentrations of potassium, glucose and lactose decreased 1.4-, 73- and 4.4-fold, respectively, over the same period of time. The changes in the milk composition showed no significant correlation to the infant's suckling frequency. The results indicate a progressive loss of secretory activity by the mammary gland during weaning and early gestation. During weaning this loss appears to be directly related to the decrease in the infant's suckling frequency, whereas during early gestation there would appear to be an inhibition of milk secretion which over-rides the positive stimulus provided by the infant's suckling. The mechanisms regulating the secretion of milk during weaning and pregnancy are discussed in the light of the compositional changes observed.

Breast↗
PubMed1984

Physiological basis of longitudinal changes in human milk yield and composition.

Currently in Western Australia more than 85% of women are breast-feeding after discharge from the hospital. Breast milk is the only fluid consumed by 64% of infants at 6 months of age, and 25% of infants are still breast-fed at 12 months of age. Therefore, many Western Australian mothers have optimized the art of breast-feeding and thereby provide an ideal population for studies of the physiological, pathological, and pharmacological factors affecting lactation. Reports from other countries conclude that the maximum milk yield of well-nourished women is 700-900 ml/24 h. Our studies have found the average milk yield of mothers breast-feeding single infants was in excess of 1100 ml/24 h for the first 6 months of lactation. Furthermore, mothers breast-feeding twins produced in excess of 2100 ml/24 h over this period, which demonstrates that the potential milk yield for mothers is much higher than 700-900 ml/24 h. Substantial alterations in the composition of breast milk occur at the initiation of lactation and after the cessation of suckling. During established lactation it is generally believed that there is only a slight variation in the composition of the milk. However, intensive studies have revealed acute changes in the concentrations of lactose, glucose, sodium, potassium, and chloride 5-6 days before and 6-7 days after ovulation. These findings suggest that unknown hormonal events associated with the reproductive cycle in women also influence breast milk composition.

Australia↗