scholarly journals Serum IGF-I Is Not a Reliable Pharmacodynamic Marker of Exogenous Growth Hormone Activity in Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4764-4776 ◽  
Author(s):  
Maximilian Bielohuby ◽  
Michael Schaab ◽  
Moritz Kummann ◽  
Mandy Sawitzky ◽  
Rolf Gebhardt ◽  
...  

Serum IGF-I is a well-established pharmacodynamic marker of GH administration in humans and has been used for this purpose in animal studies. However, its general suitability in wild-type laboratory mice has not been demonstrated. Here we show that treatment with recombinant human GH (rhGH) in four different strains of laboratory mice increases body weight, lean body mass, and liver weight but does not increase hepatic expression and release of IGF-I. In contrast and as expected, hypophysectomized rats show a rapid increase in serum IGF-I after rhGH administration. The lack of IGF-I up-regulation in mice occurs despite hepatic activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and is not explained by GH dose, route of administration, origin of GH (i.e. recombinant human, bovine, and murine GH), treatment duration, genetic background, sex, or formation of neutralizing antibodies. Effects on other components of the GH/IGF pathway were highly influenced by genetic background and sex but not consistently affected by rhGH treatment. We conclude that IGF-I is not a reliable indicator of the biological effects of exogenous GH treatment in genetically and pharmacologically unmodified mice. We speculate that IGF-I release is already maximal in these animals and cannot be further increased by exogenous GH treatment. This is also suggested by the observation of restored IGF-I up-regulation in isolated murine hepatocytes after rhGH treatment. Total body weight, lean body mass, and liver weight may be more reliable phenotypic indicators in these models.

2001 ◽  
Vol 22 (6) ◽  
pp. 787-799 ◽  
Author(s):  
Pia Burman ◽  
E. Martin Ritzén ◽  
Ann Christin Lindgren

Abstract Prader-Willi syndrome is a genetic disorder occurring in 1 in 10,000–16,000 live-born infants. In the general population, approximately 60 people in every 1,000,000 are affected. The condition is characterized by short stature, low lean body mass, muscular hypotonia, mental retardation, behavioral abnormalities, dysmorphic features, and excessive appetite with progressive obesity. Furthermore, morbidity and mortality are high, probably as a result of gross obesity. Most patients have reduced GH secretory capacity and hypogonadotropic hypogonadism, suggesting hypothalamic-pituitary dysfunction. Replacement of GH and/or sex hormones may therefore be beneficial in Prader-Willi syndrome, and several clinical trials have now evaluated GH replacement therapy in affected children. Results of GH treatment have been encouraging: improved growth, increased lean body mass, and reduced fat mass. There was also some evidence of improvements in respiratory function and physical activity. The long-term benefits of GH treatment are, however, still to be established. Similarly, the role of sex hormone replacement therapy needs to be clarified as few data exist on its efficacy and potential benefits. In summary, Prader-Willi syndrome is a disabling condition associated with GH deficiency and hypogonadism. More active treatment of these endocrine disorders is likely to benefit affected individuals.


Author(s):  
Francesco Di Sabato ◽  
Pamela Fiaschetti ◽  
Carlina V. Albanese ◽  
Roberto Passariello ◽  
Filippo Rossi Fanelli ◽  
...  
Keyword(s):  

2002 ◽  
Vol 57 (3) ◽  
pp. 107-114 ◽  
Author(s):  
Pauline L. Martin ◽  
Joan Lane ◽  
Louise Pouliot ◽  
Malcolm Gains ◽  
Rudolph Stejskal ◽  
...  

1988 ◽  
Vol 74 (2) ◽  
pp. 107-114
Author(s):  
D. J. Smith ◽  
R. J. Pethybridge ◽  
A Duggan

SummaryThe relationship between physical fitness, anthropometric measures, and the scores in three submaximal step tests have been evaluated in a group of 30 male subjects. Physical fitness was assessed as VO2max measured directly during uphill treadmill running. Each submaximal exercise test was of six minutes duration and the heart rate recorded during the last minute (fH6) constituted the test score. Significant negative correlation coefficients were found between VO2max and each test score while lean body mass, gross body weight and body surface area were allpositively correlated with VO2max (1/min). The score in the least severe step test was included with anthropometric measures in multiple linear regression analysis for the prediction of VO2max and a number of prediction equations were derived. It was found that when lean body mass is calculated from skinfold measurements and weight, VO2max can be calculated from the equation:VO2max(1/min) = 1.470 + 0.0614 × Lean Body mass −0.0131 × fH6This equation accounts for 73% of the total variation of VO2max. If lean body mass cannot be calculated, a combination of gross body weight and age plus fH6 gives the equation:VO2max = 3.614 + 0.0349 × Weight – 0.0177 × fH6−0.0161 × Ageaccounting for 66% of the variance. The test has the following advantages over those currently employed:It is simple to administer requiring 6 minutes of stepping onto a 32 cm platform—the height of a gymnasium bench—20 times per minute.Although ideally an assessment oflean body mass is required, gross body weight plus age is a good second best.It is submaximal, minimising the stress on the individual (mean heart rate achieved 121 beats per minute).Its accuracy in terms of its ability to predict maximal aerobic power is better than either the Ohio or Harvard University tests.It is suggested that this test could be used where maximal testing is contraindicated or where currently used tests are insufficiently accurate.


1965 ◽  
Vol 20 (5) ◽  
pp. 934-937 ◽  
Author(s):  
ŠtĚpánka Šprynarová ◽  
Jana Pařízková

Seven obese boys submitted themselves to a 7-week regimen of dietary restriction and regular exercise. Measurements were made at the beginning and end of the period. A significant drop in body weight was achieved by reduction of adipose tissue and also of lean body mass (LBM). The ratio of LBM to body weight increased. These changes were associated with significant drop of maximum oxygen consumption. The increase of the Vo2 max per kilogram of body weight and the drop of the Vo2 max per kilogram of LBM were not significant. Between the decrease of LBM and the drop of Vo2 max there exists a significant negative relationship; and between the decrease of LBM and the rise of the Vo2 max per kilogram of body weight, a significant positive relationship. The decrease of Vo2 max in these boys was not considered due to deteriorated circulatory or respiratory function but to changes in body composition. maximum O2 consumption; body weight reduction; lean body mass Submitted on February 17, 1964


1977 ◽  
Vol 43 (1) ◽  
pp. 126-132 ◽  
Author(s):  
J. E. Greenleaf ◽  
E. M. Bernauer ◽  
L. T. Juhos ◽  
H. L. Young ◽  
J. T. Morse ◽  
...  

To determine the cause of the body weight loss during bed rest (BR), fluid balance and anthropometric measurements were taken from seven men (19–21 yr) during three 2-wk BR periods which were separated by 3-wk ambulatory recovery periods. Caloric intake was 3,073 +/- 155 (SD) kcal/day. During two of the three BR periods they performed supine isotonic exercise at 68% of VO2max on the ergometer for 1 h/day; or supine isometric exercise at 21% of maximal leg extension force for 1 min followed by a 1-min rest for 1 h/day. No prescribed exercise was given during the other BR period. During BR, body weight decreased slightly with no exercise (-0.43 kg, NS), but decreased significantly (P less than 0.05) by -0.91 kg with isometric and by -1.77 kg with isotonic exercise. About one-third of the weight reduction with isotonic exercise was due to fat loss (-0.69 kg) and, the remainder, to loss of lean body mass (-0.98 kg). It is concluded that the reduction in body weight during bed rest has two major components: First, a loss of lean body mass caused by assumption of the horizontal body position that is independent of the metabolic rate. Second, a loss of body fat content that is proportional to the metabolic rate.


2006 ◽  
Vol 91 (11) ◽  
pp. 4302-4305 ◽  
Author(s):  
Mim Ari ◽  
Vladimir K. Bakalov ◽  
Suvimol Hill ◽  
Carolyn A. Bondy

Abstract Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. Results: The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1–14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1–L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.


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