scholarly journals Responses to divergent selection for plasma concentrations of insulin-like growth factor-1 in mice

1989 ◽  
Vol 53 (3) ◽  
pp. 187-192 ◽  
Author(s):  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
J. E. Ormsby ◽  
...  

SummaryA divergent selection experiment with mice, using plasma concentrations of insulin-like growth factor-1 (IGF-1) at 42 days of age as the selection criterion, was undertaken for 7 generations. Lines were not replicated. To obtain sufficient plasma for the IGF-1 assay, blood from four individuals was volumetrically bulked to obtain a litter mean IGF-1 concentration. This necessitated the use of between family selection. Although inbreeding accumulated in a linear fashion in each of the high, control and low lines, the rates were different for each line (3·6, 1·6 and 5·3% per generation for the high, control and low lines, respectively). As a consequence, the effects of selection and inbreeding are confounded in this experiment. Divergence between the high and low lines in plasma concentrations of IGF-1 continued steadily until generation 5. In generations 6 and 7, there was a reduced degree of divergence and this contributed towards the low realized heritability value of 0.15 ± 0.12. Six-week liveweight showed a steady positive correlated response to selection for or against plasma concentrations of IGF-1 until generation 4 (high-low difference = 1·7 g = 12%). In generation 5, a substantial drop in 6-week liveweight in the low line relative to both the high and control lines occurred (high-low difference, 3·9; g, 25%). This difference was maintained until generation 7.This experiment suggests that genetic variation exists at 6 weeks of age in plasma concentrations of IGF-1 in mice. Furthermore, genetic covariation between plasma IGF-1 concentrations and liveweight at 6 weeks of age is likely to be positive. Further experiments have been initiated to examine these theories.

1994 ◽  
Vol 59 (2) ◽  
pp. 251-262 ◽  
Author(s):  
N. D. Cameron

AbstractResponses to four generations of divergent selection for lean groivth rate with ad-libitum feeding (LGA), for lean food conversion (LFC) and for daily food intake (DFI) in Large White pigs were studied. The LGA (LFC) selection criterion was designed to obtain equal correlated responses in growth rate (food conversion ratio) and carcass lean content, measured in phenotypic s.d. The selection criteria had phenotypic s.d. of 27, 29 and 253 units, respectively, and results are presented in s.d. units. There was a total of 3537 pigs, with an average of 40 boars and 40 gilts performance tested in each of the high, low and control lines per generation and the lines consisted of 10 sires and 20 dams. The generation interval was equal to 13·5 months. Animals were performance tested in individual pens with mean starting and finishing weights of 30 kg and 85 kg respectively.Cumulative selection differentials in the three selection groups were 5·8, 3·6 and 3·3 phenotypic s.d. for LGA, LFC and DFI respectively. Direct responses to divergent selection were 1·7, 1·3 and 1·2 (s.e. 0·17) for LGA, LFC and DFI. The correlated response in LFC (1·6 (s.e. 0·18)) with selection on LGA was greater than the direct response in LFC. Conversely, the direct response in LGA was greater than the correlated response (1·1 (s.e. 0·18)) with selection on LFC. The response in LFC (–1·1 (s.e. 0·17)) with selection on DFI was similar in size but opposite in sign to the direct response in LFC. Responses were asymmetric about the control, as the high LGA and LFC responses were proportionately smaller (0·74 and 0·58) than low line responses. In contrast, the difference between the high DFI and control was four times greater than the difference between low line and control.Heritabilities of LGA, LFC and DFI were 0·38, 0·35 and 0·29 (s.e. 0·03), when estimated by residual maximum likelihood, with common environmental effects of 0·09 (s.e. 0·02). Genetic correlations for LGA with LFC and DFI were positive, 0·76 (s.e. 0·03) and 0·23 (s.e. 0·07), but the genetic correlation between DFI and LFC was negative, –0·45 (s.e. 0·06). The experiment demonstrated that substantial responses to selection can be achieved in LGA, LFC and DFI. Selection on LGA resulted in larger direct and correlated responses than selection on LFC.


1996 ◽  
Vol 150 (1) ◽  
pp. 121-127 ◽  
Author(s):  
C G Prosser ◽  
J Schwander

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


Author(s):  
Nilgün Gültiken ◽  
Murat Yarim ◽  
Gül Fatma Yarim ◽  
Mahmut Sözmen ◽  
Elvan Anadol ◽  
...  

AbstractThe objective of this study was to investigate the plasma concentrations of insulin-like growth factor-2 (IGF-2) as well as its expression in the uterus and ovary of healthy dogs and those with cystic endometrial hyperplasia (CEH)–pyometra complex. Group 1 (n = 10) included bitches with open cervix pyometra, while Group 2 (n = 7) consisted of clinically healthy bitches in dioestrus. The number of IGF-2 immunopositive interstitial cells was significantly higher in Group 1, whereas in Group 2 there were only two cases in which a few cells were IGF-2 immunopositive. IGF-2 immunopositivity was observed in the endometrial glandular epithelium in both groups. Additionally, interstitial fibroblasts and macrophages in the endometrium were also positive in Group 1. The concentration of plasma IGF-2 was higher in Group 1 than in Group 2 (P < 0.05). The concentration was positively correlated with IGF-2 expression in the endometrial glands (r = 0.926; P < 0.001) in Group 1. However, a negative correlation was present between plasma IGF-2 concentration and IGF-2 expression in the interstitial endocrine cells of the ovary in Group 1 (r = −0.652; P < 0.05). The results suggest that IGF-2 plays an important role during the inflammatory process occurring in bitches with CEH–pyometra complex as well as in the endometrium of healthy bitches in dioestrus.


1991 ◽  
Vol 65 (1) ◽  
pp. 47-60 ◽  
Author(s):  
D. Dardevet ◽  
M. Manin ◽  
M. Balage ◽  
C. Sornet ◽  
J. Grizard

The influence of protein content of the diet on the plasma concentrations and binding to skeletal muscle and liver of insulin and insulin-like growth factor-1 (IGF-1), was studied in growing rats. Animals with a starting body-weight of 80 g received for an 11 d period isoenergetic diets containing (g/kg dry matter) 155 protein as controls (MP), or 55 (LP) or 300 (HP) protein. Food was offered as six equal meals/d. Daily food intakes provided adequate amounts of energy. Total plasma IGF-1 increased linearly as a function of dietary protein intake. Plasma insulin was lower in the LP than in the MP and HP groups. Hormone binding was studied in wheat-germ agglutinin (WGA) partially purified skeletal muscle receptor preparations. Each 125I-labelled hormone binding was competed for by increasing amounts of homologous and heterologous unlabelled hormone; this displacement needed lower concentrations of homologous than heterologous hormone. When compared with MP-diet feeding, the LP diet resulted in an increased ligand concentration for half-maximal binding. In addition the specific 125I-labelled insulin and 125I-labelled IGF-1 binding increased at all hormone concentrations and, as revealed by Scatchard analysis, the hormone binding capacity also rose (only significant for low-affinity insulin receptors and high-affinity IGF-1 receptors). The HP diet had little effect on hormone binding, except to increase insulin binding at very low insulin concentrations. Hormone binding was further studied in WGA partially purified liver receptor preparations. Those preparations did not exhibit any detectable specific 125I-labelled IGF-1 binding. The specific 125I-labelled insulin binding was not altered by dietary protein level. It is concluded that the increase in skeletal muscle insulin and IGF-1 binding along with a decrease in insulin and IGF-1 in the blood from rats fed on the LP diet, is consistent with the concept of an inverse relationship between plasma hormone and hormone binding. The physiological significance with respect to metabolic adaptation of muscle remains to be established


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