Growth hormone and insulin-like growth factor I in German Shepherd dwarf dogs

1984 ◽  
Vol 105 (3) ◽  
pp. 289-293 ◽  
Author(s):  
J. E. Eigenmann ◽  
S. Zanesco ◽  
U. Arnold ◽  
E. R. Froesch

Abstract. The roles of growth hormone (GH) and insulin-like growth factor I (IGF I) were studied in 9 German Shepherd dwarf dogs. GH deficiency was evidenced in all dogs by an absence of increase in GH levels in response to clonidine administration. While the mean IGF I concentration in normal adult German Shepherds was 280 ± 23 ng/ml and 345 ± 50 ng/ml in immature animals, the mean IGF I concentration in the dwarf dogs was 11 ± 2 ng/ml (mean ± sem, P < 0.001). In the affected animals, plasma thyroxine (T4) levels were only slightly subnormal and there was an increase in these levels in response to thyroid stimulating hormone (TSH) administration. The findings indicate 1) that dwarfism in German Shepherds is caused by primary GH-deficiency resulting in low circulating levels of IGF I and 2) that IGF I levels in the dog as in man are subject to control by GH.

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.


1996 ◽  
Vol 134 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Yukihiro Hasegawa ◽  
Tomonobu Hasegawa ◽  
Makoto Takada ◽  
Yutaka Tsuchiya

Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184–9. ISSN 0804–4643. Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the f IGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid–ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5th percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Urnezono Kiyose, Tokyo 204, Japan


1984 ◽  
Vol 105 (3) ◽  
pp. 294-301 ◽  
Author(s):  
J. E. Eigenmann ◽  
D. F. Patterson ◽  
J. Zapf ◽  
E. R. Froesch

Abstract. A radioimmunoassay (RIA) devised for the measurement of human insulin-like growth factor I (IGF I) was employed for the measurement of canine IGF I. Canine IGF I was extracted from plasma specimens by gel chromatography. Columns were eluted with 1 m acetic acid and the fractions representing the 55 to 85% bed volume were pooled, lyophilized and reconstituted with assay buffer. Serial dilutions of canine IGF I from both normal and acromegalic dogs when added to the RIA system gave a similar displacement pattern of human [125I]IGF I as the one obtained by the addition of unlabelled human IGF I. The dose-response curve obtained by canine IGF I paralleled the one obtained by human IGF I. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.039 and 5 ng IGF I added per tube. The within-assay coefficient of variation (CV) was 16.7% and the between-assay CV was 21.8%. Plasma IGF I concentrations in normal dogs appeared to be a function of body size. The concentrations were 36 ± 27 ng/ml in Cocker Spaniels, 87 ± 33 ng/ml in Beagles, 117 ± 34 ng/ml in Keeshonds, and 280 ± 23 ng/ml in German Shepherds (mean ± sem). The mean IGF I level in a group of dogs with growth hormone (GH) elevation was 700 ± 90 ng/ml. Though this group of dogs comprised both small and large dogs, the mean IGF I level significantly differed from the one found in German Shepherds, the largest breed studied (P < 0.01). IGF I levels in dogs with GH elevation were similarly elevated in both dogs exhibiting acromegaly and dogs exhibiting GH-diabetes, but no signs of acromegaly. In dogs with GH elevation, drop in GH levels was associated with a significant drop in IGF I levels.


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


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