Identification of insulin-like growth factor-I and its receptors in the rat testis

1985 ◽  
Vol 109 (4) ◽  
pp. 543-549 ◽  
Author(s):  
D. J. Handelsman ◽  
J. A. Spaliviero ◽  
C. D. Scott ◽  
R. C. Baxter

Abstract. As part of a study of the testicular production and action of insulin-like growth factor-I (IGF-I), adult rat testes were extracted with acidified methanol, yielding an immunoreactive IGF-I fraction corresponding in size to human IGF-I. The mean IGF-I content (± sem) of testes weighing approximately 1.1 g was 51.5 ± 5.6 ng/testis, and was not due to serum contamination. After a 3-day fast testicular IGF-I decreased by 80%, whereas serum IGF-I levels declined by 90%. Testicular homogenates and isolated Leydig cells were shown to contain specific IGF-I receptors, Ka = 2 × 109 m−1, with 10% IGF-II cross-reactivity. The concentration of these receptors was 2 pmol binding sites per testis, or 3.3 fmol per 106 Leydig cells. However IGF-I at 250 ng/ml had no effect on basal or hCG-stimulated testosterone production by isolated Leydig cells, measured over 3 h. Although an effect of IGF-I over longer incubation periods cannot be excluded, it is also possible that testicular IGF-I has a mitogenic role, rather than acting on differentiated testicular functions.

1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204


1988 ◽  
Vol 119 (3) ◽  
pp. 333-338 ◽  
Author(s):  
A. Silbergeld ◽  
L. Jaber ◽  
P. Lilos ◽  
Z. Laron

Abstract. Insulin-like growth factor I levels were measured in a parallel fashion in 77 extracted sera using the INCSTAR RIA (radioimmunoassay) and in the EDTA plasma of the same subjects by the NICHOLS RIA. The subjects suffered from untreated hGH deficiency, short stature, delayed and precocious puberty and acromegaly. Significant differences (P < 0.05) were found between the mean IGF-I levels of all groups using both RIA systems. However, using the INCSTAR RIA, 85% of IGF-I values in untreated hGH deficiency were below normal, and a rise in IGF-I detected in the sera of all 5 patients who were treated with hGH. Using NICHOLS RIA, 55% of basal IGF-I values were below normal and a hGH-stimulated rise in IGF-I was found in only two of the treated patients. The INCSTAR RIA seems more precise and reproducible than the NICHOLS RIA and enables better discrimination of hGH-deficient patients from age-matched controls.


2006 ◽  
Vol 105 (6) ◽  
pp. 843-852 ◽  
Author(s):  
Jimmi Hatton ◽  
Richard Kryscio ◽  
Melody Ryan ◽  
Linda Ott ◽  
Byron Young

Object Hypermetabolism, hypercatabolism, refractory nitrogen wasting, hyperglycemia, and immunosuppression accompany traumatic brain injury (TBI). Pituitary dysfunction occurs, affecting growth hormone (GH) and plasma insulin-like growth factor–I (IGF-I) concentrations. The authors evaluated whether combination IGF-I/GH therapy improved metabolic and nutritional parameters after moderate to severe TBI. Methods The authors conducted a prospective, randomized, double-blind study comparing combination IGF-I/GH therapy and a placebo treatment. Ninety-seven patients with TBI were enrolled in the study within 72 hours of injury and were assigned to receive either combination IGF-I/GH therapy or placebo. All patients received concomitant nutritional support. Insulin-like growth factor–I was administered by continuous intravenous infusion (0.01 mg/kg/hr), and GH (0.05 mg/kg/day) was administered subcutaneously. Placebo control group patients received normal saline solution in place of both agents. Nutritional and metabolic monitoring continued throughout the 14-day treatment period. The two groups did not differ in energy expenditure, nutrient intake, or use of insulin treatment. The mean daily serum glucose concentration was higher in the treatment group (123 ± 24 mg/dl) than in the control group (104 ± 11 mg/dl) (p < 0.03). A positive nitrogen balance was achieved within the first 24 hours in the treatment group and remained positive in that group throughout the treatment period (p < 0.05). This pattern was not observed in the control group. Plasma IGF-I concentrations were above 350 ng/ml in the treatment group throughout the study period. Overall, the mean plasma IGF-I concentrations were 1003 ± 480.6 ng/ml in the treatment group and 192 ± 46.2 ng/ml in the control group (p < 0.01). Conclusions The combination of IGF-I and GH produced sustained improvement in metabolic and nutritional endpoints after moderate to severe acute TBI.


1992 ◽  
Vol 135 (2) ◽  
pp. 171-174 ◽  
Author(s):  
F. Aguado ◽  
F. Sánchez-Franco ◽  
L. Cacidedo ◽  
T. Fernández ◽  
J. Rodrigo ◽  
...  

1987 ◽  
Vol 114 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Ines Zangger ◽  
Jürgen Zapf ◽  
E. Rudolf Froesch

Abstract. Insulin-like growth factor I and II (IGF I and II) were determined by five different assays in human serum, in the sera of ten mammalian species and in chicken, turtle, and frog serum. Sera of all tested mammals contain two different IGFs corresponding to human immunoreactive IGF I and receptor reactive IGF II. Receptor reactive IGF II of most animal species does not show significant cross-reactivity in the RIA for human IGF II. IGF activity was also detected in sera of non-mammals, such as chicken and turtles, but not in frog serum. The IGF values obtained with the different assay system corresponded rather well: there is a good correlation between the values obtained in the protein binding and the fat cell assay, and between the results of the latter assays and the sum of immunoreactive IGF I and receptor reactive IGF II. The results suggest that those regions in the IGF I and II molecules which are responsible for reactivity with the type I IGF and the insulin receptor have not essentially changed during evolution. Similarly, the C-region, which mainly determines the immunological properties of IGFs, appears to have remained relatively constant in the IGF I, but not in the IGF II molecule.


Author(s):  
Kenneth Maleta ◽  
Yue-Mei Fan ◽  
Juho Luoma ◽  
Ulla Ashorn ◽  
Jaden Bendabenda ◽  
...  

ABSTRACT Background Insulin-like growth factor I (IGF-I) is the most important hormonal promoter of linear growth in infants and young children. Objectives The objectives of this study were to compare plasma IGF-I concentration in a low- compared with a high-income country and characterize biological pathways leading to reduced IGF-I concentration in children in a low-income setting. Methods We analyzed plasma IGF-I concentration from 716 Malawian and 80 Finnish children at 6–36 mo of age. In the Malawian children, we studied the association between IGF-I concentration and their environmental exposures; nutritional status; systemic and intestinal inflammation; malaria parasitemia and viral, bacterial, and parasitic enteric infections; as well as growth at 18 mo of age. We then conducted a pathway analysis to identify direct and indirect associations between these predictors and IGF-I concentration. Results The mean IGF-I concentrations were similar in Malawi and Finland among 6-mo-old infants. At age 18 mo, the mean ± SD concentration was almost double among the Finns compared with the Malawians [24.2 ± 11.3 compared with 12.5 ± 7.7 ng/mL, age- and sex-adjusted difference in mean (95% CI): 11.8 (9.9, 13.7) ng/mL; P &lt; 0.01]. Among 18-mo-old Malawians, plasma IGF-I concentration was inversely associated with systemic inflammation, malaria parasitemia, and intestinal Shigella, Campylobacter, and enterovirus infection and positively associated with the children's weight-for-length z score (WLZ), female sex, maternal height, mother's education, and dry season. Seasonally, mean plasma IGF-I concentration was highest in June and July and lowest in December and January, coinciding with changes in children's length gain and preceded by ∼2 mo by the changes in their WLZ. Conclusions The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways.


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