Comparison of the effects of administration of recombinant bovine growth hormone or N-Met insulin-like growth factor-I to lactating goats

1989 ◽  
Vol 123 (1) ◽  
pp. 33-39 ◽  
Author(s):  
S. R. Davis ◽  
P. D. Gluckman ◽  
S. C. Hodgkinson ◽  
V. C. Farr ◽  
B. H. Breier ◽  
...  
Keyword(s):  
Growth Factor ◽  
Milk Yield ◽  
Plasma Concentrations ◽  
Physiological Saline ◽  
Experimental Period ◽  
Yield Response ◽  
Insulin Like Growth Factor ◽  
Lactating Goats ◽  
Igf I ◽  
Sustained Increase

ABSTRACT Five goats were injected with GH (15 mg/day), three goats received systemic infusions of insulin-like growth factor (IGF)-I (43 nmol/h) and four goats received systemic infusions of physiological saline (20 ml/h) on days 4–6 of a 10-day experimental period during mid-lactation. Milk yield increased by an average of 24% in GH-treated goats by the time of the third injection. In contrast, milk yield of IGF-I-infused goats did not differ from saline-infused animals although two of three goats did show a small increase (12%) after 36 h of IGF-I infusion. With GH and IGF-I treatments plasma IGF-I concentrations increased similarly, reaching maxima of 100–130 nmol/l within 24 h. Plasma IGF-I concentration was relatively constant in saline-infused goats at about 50 nmol/l throughout the experiment. Total IGF-I bound to 50 kDa and 150 kDa binding proteins in plasma was increased by GH and IGF-I treatments but, in contrast to IGF-I, GH increased the proportion of IGF-I bound to 150 kDa binding protein. In a second experiment, four goats received systemic infusion of IGF-I (43 nmol/h) and four goats received systemic infusion of physiological saline (20 ml/h). There was no evidence that milk yield was changed during IGF-I infusion. However, when those goats which had previously received IGF-I infusions were injected with GH, milk yield increased by 30%. While the increment in plasma IGF-I concentration during IGF-I infusion was similar to that obtained in the first experiment, the IGF-I response to GH injection was much greater, plasma concentrations rising to 230 nmol/l. The data show a lack of milk yield response in goats whose plasma IGF-I concentrations were increased by IGF-I administration. Systemic infusion of IGF-I appears to be ineffective as a means of procuring a sustained increase in milk production. Journal of Endocrinology (1989) 123, 33–39

Effects of close-arterial (external pudic) infusion of insulin-like growth factor-II on milk yield and mammary blood flow in lactating goats

1994 ◽  
Vol 142 (1) ◽  
pp. 93-99 ◽  
Author(s):  
C G Prosser ◽  
S R Davis ◽  
V C Farr ◽  
L G Moore ◽  
P D Gluckman
Keyword(s):  
Blood Flow ◽  
Growth Factor ◽  
Milk Yield ◽  
Yield Response ◽  
Mammary Tissue ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Lactating Goats ◽  
Factor Ii ◽  
Igf I

Abstract Five lactating goats were infused, via an external pudic arterial catheter, directly into the mammary gland with 0·9% (w/v) NaCl (20 ml/h), recombinant human insulin-like growth factor-I (IGF-I; 80 nmol/h), recombinant human IGF-II (133 nmol/h) or IGF-I and IGF-II combined. The infusion was for 6 h and milk yield was determined every 2 h. The ratio of milk yield in the infused relative to the non-infused gland was changed only slightly by saline (2%), but increased to 9% (P<0·05) in response to IGF-I and 8% (P<0·05) in response to IGF-II. When combined, both peptides increased this ratio by 6%. These effects were elicited within 2–4 h of the beginning of infusion. Mammary blood flow increased 50–80% (P<0·05) during all IGF infusions, but only 28% during saline treatment. Plasma insulin decreased 50% (P<0·01) during the infusion of IGF-I alone or in combination with IGF-II and 25% in response to IGF-II alone. Whereas plasma glucose increased by approximately 10% during infusion of IGF-I alone or with IGF-II, it was not altered by infusion of IGF-II only. The rapidity and unilateral nature of the milk-yield response to IGF-I and IGF-II is consistent with their acting directly on mammary tissue itself. Thus, the present results demonstrate similar local and systemic actions induced by intramammary infusion of IGF-II and IGF-I, although the magnitude of the response to IGF-II tends to be less than that to IGF-I. Journal of Endocrinology (1994) 142, 93–99

Influence of insulin-like growth factor-binding protein-2 on plasma clearance and transfer of insulin-like growth factors-I and -II from plasma into mammary-derived lymph and milk of goats

1996 ◽  
Vol 150 (1) ◽  
pp. 121-127 ◽  
Author(s):  
C G Prosser ◽  
J Schwander
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Plasma Clearance ◽  
Binding Protein ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Lactating Goats ◽  
Igf I ◽  
Insulin Like Growth Factors

Abstract Plasma clearance of insulin-like growth factors-I and -II (IGF-I and -II) and insulin-like growth factor-binding protein-2 (IGFBP-2) from lactating goats (n=4) was determined following a single intravenous injection of the corresponding 125I-labelled human protein. Transfer of these proteins out of the vascular space was monitored by their subsequent appearance in mammary-derived lymph and milk. Clearance of 125I-IGFBP-2 from circulation was 0·37 ± 0·06 ml/min/kg, which is markedly greater than that of 125I-IGF-I or -II (0·11 ± and 0·12 ± 0·01 ml/min/kg respectively). This was also reflected in longer elimination half-lives for IGF-I (353 ± 6 min) and -II (254 ± 8 min) compared with IGFBP-2 (110 ± 9 min). Three hours after injection of the 125I-labelled protein, the plasma:lymph ratio of trichloroacetic acid-precipitable radioactivity was 1·54 ±0·04, 3·3 ±0·6 and 4·1 ±0·4 for IGFBP-2, IGF-I and -II respectively. The form of 125I-IGFBP-2 in lymph was not different from that of plasma. Elevation of plasma concentrations of IGFBP-2 by its intravenous infusion significantly decreased plasma half-life of both IGF-I and -II (251 ± 8 and 198 ±7 min respectively). Although the amount and rate of transfer of IGF into mammary-derived lymph was decreased slightly by IGFBP-2, concentrations eventually obtained were not different from control. However, secretion of IGFs into milk was significantly reduced by IGFBP-2, particularly in the case of IGF-I. These results are consistent with the ability of all three compounds to cross the vascular endothelium intact and of IGFBP-2 to decrease the uptake of IGF by mammary epithelium and subsequent secretion into milk. IGFBP-2 may well have acted to target plasma IGF towards non-mammary tissues, thus explaining the more rapid plasma clearance of IGFs in the presence of elevated IGFBP-2. Journal of Endocrinology (1996) 150, 121–127

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

1989 ◽  
Vol 56 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Colin G. Prosser ◽  
Ivan R. Fleet ◽  
Anthony N. Corps
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Milk Yield ◽  
Plasma Concentrations ◽  
Significant Proportion ◽  
Bovine Growth Hormone ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

SummarySix 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 7d preceding treatment. Concentrations of insulin-like growth factor I (IGF-I) in the milk increased from 0·44 ± 0·04 nmol/1 (mean ± s. e. m.) during the 7 d preceding treatment to 1·6 ± 0·2 nmol/1 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/1 (mean ± s. e. m.) on the day preceding treatment to 56·9 ± 3·6 nmol/1 (mean ± s. e. m.) on d 7 of treatment. Mammary plasma flow increased from 1·6 ± 0·09 to 2·2 ± 0·06 1/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 40000 to 150000 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 31000 mol. wt.

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

1991 ◽  
Vol 131 (3) ◽  
pp. 459-466 ◽  
Author(s):  
C. G. Prosser ◽  
I. R. Fleet ◽  
A. J. Davis ◽  
R. B. Heap
Keyword(s):  
Growth Factor ◽  
Time Course ◽  
Specific Activity ◽  
Gel Filtration ◽  
Free Form ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Lactating Goats ◽  
Igf I ◽  
Growth Factor I

ABSTRACT 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. Comparison of uptake and secretion of 125I-labelled IGF-I into milk from the non-infused gland with that of endogenous immunoreactive IGF-I suggests that vectorial transport of IGF-I across the mammary gland may be a significant contributor of IGF-I levels in milk. Journal of Endocrinology (1991) 131, 459–466

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

Blood Plasma Concentrations of Insulin-like Growth Factor-I (IGF-I) in Resting Standardbred Horses

2002 ◽  
Vol 163 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Z.J. Champion ◽  
B.H. Breier ◽  
W.E. Ewen ◽  
T.T. Tobin ◽  
P.J. Casey
Keyword(s):  
Growth Factor ◽  
Blood Plasma ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Intravenous infusion of insulin-like growth factor I in fetal sheep reduces hepatic IGF-I and IGF-II mRNAs

1996 ◽  
Vol 271 (6) ◽  
pp. R1632-R1637 ◽  
Author(s):  
K. L. Kind ◽  
J. A. Owens ◽  
F. Lok ◽  
J. S. Robinson ◽  
K. J. Quinn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Intravenous Infusion ◽  
Feedback Inhibition ◽  
Fetal Liver ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Fetal Sheep ◽  
Igf I

Liver contains the highest concentrations of insulin-like growth factor (IGF) I mRNA in adult rats and sheep and is a major source of circulating IGF-I. In rats, inhibition of hepatic IGF-I production by exogenous IGF-I has been reported. In fetal sheep, skeletal muscle and liver are major sites of IGF-I synthesis and potential sources of circulating IGF-I. To determine whether feedback inhibition of IGF gene expression in fetal liver or muscle by IGF-I occurs, IGF-I and IGF-II mRNAs were measured in these tissues after intravenous infusion of recombinant human IGF-I into fetal sheep. Infusion of IGF-I (26 +/- 4 micrograms.h-1.kg-1; n = 6) or saline (n = 6) commenced on day 120 of pregnancy (term = 150 days) and continued for 10 days. Plasma concentrations of IGF-I were threefold higher in infused fetuses at 130 days of gestation (P < 0.0003), whereas those of IGF-II were unchanged. IGF-I infusion reduced the relative abundance of IGF-I mRNA (P < 0.0002) and IGF-II mRNA (P < 0.01) in fetal liver by approximately 50% but did not alter IGF-I or IGF-II mRNA in skeletal muscle. These results indicate that IGF-I inhibits the expression of both IGF-I and IGF-II genes in fetal liver and that IGF gene expression in fetal liver and muscle is differentially regulated by IGF-I.

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I

1990 ◽  
Vol 124 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. A. Siddiqui ◽  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Plasma Concentrations ◽  
Body Growth ◽  
Insulin Like Growth Factor ◽  
Developmental Patterns ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P<0·05) but not by sex. Significant (P< 0·001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P< 0·001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant. Nose–anus length was significantly (P<0·01) affected by sex and line from 42 to 105 days of age, but anus–tail length was not affected by sex or line at any age. Effects of sex and line on empty (digesta-free) body weight and wet weights of carcass and skin plus viscera fractions followed a pattern similar to those of liveweights. The effects of sex and line on protein, water and fat content also paralleled their effects on body size. Differences between males and females, and between the lines, in amount of protein, water and fat could be entirely accounted for by the corresponding differences in body weight. It is concluded from these results that divergent selection on the basis of plasma IGF-I at 42 days of age resulted in lines of animals differing in plasma IGF-I from 21 days of age until maturity. These divergent concentrations of IGF-I are associated with differences between the lines in body growth, particularly during the period of accelerated growth at puberty, but not with changes in body composition. Journal of Endocrinology (1990) 124, 151–158

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