Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats

1994 ◽  
Vol 130 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Katharina Binz ◽  
Christoph Schmid ◽  
Roger Bouillon ◽  
E Rudolf Froesch ◽  
Kay Jürgensen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Density ◽  
Trabecular Bone ◽  
Mineral Metabolism ◽  
Male Rats ◽  
Insulin Like Growth Factor ◽  
Trabecular Bone Density ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Binz K, Schmid C, Bouillon R, Froesch ER, Jürgensen K, Hunziker EB. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur J Endocrinol 1994;130:387–93. ISSN 0804–4643 Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 μg/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters. We conclude that IGF I-infusion in male rats treated with high doses of dexamethasone reduces insulin resistance and restores calcitriol production but not osteoblast function or responsiveness to calcitriol. K Binz, Division de Diabétologie, Hôpital Cantonal Universitaire, 1211 Geneva, Switzerland

Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats

1994 ◽  
Vol 267 (1) ◽  
pp. E1-E6 ◽  
Author(s):  
K. Mueller ◽  
R. Cortesi ◽  
D. Modrowski ◽  
P. J. Marie
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Ovariectomized Rats ◽  
Maximal Effect ◽  
Insulin Like Growth Factor ◽  
Bone Formation Rate ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Although in vitro experiments indicate that insulin-like growth factor I (IGF-I) is an anabolic hormone in bone cell metabolism, the effects of IGF-I in vivo on bone formation are unclear. We thus investigated whether IGF-I is able to stimulate bone formation in adult rats with established osteopenia induced by ovariectomy (OVX). IGF-I was administered at daily doses of 0.05, 0.2, and 0.8 mg/kg for 3 wk. OVX induced a marked osteopenia in femur and tibia. Administration of IGF-I increased trabecular bone mass with a maximal effect at 0.2 mg/kg. The same dose stimulated bone formation, as revealed by an increase in osteoid surface, osteoblast surface, triple tetracycline-labeled surface, and bone formation rate. The mineral apposition rate was equally stimulated at all doses. At the highest dose, IGF-I increased osteoclast surface and osteoclast number. These data indicate that, in the adult OVX rat, IGF-I stimulates bone formation and increases trabecular bone volume at medium doses and enhances the histological indexes of bone resorption at high doses.

Regulation of testicular insulin-like growth factor-I in pubertal growth hormone-deficient male rats

1991 ◽  
Vol 131 (2) ◽  
pp. 279-285 ◽  
Author(s):  
J. Spiteri-Grech ◽  
J. M. S. Bartlett ◽  
E. Nieschlag
Keyword(s):  
Growth Factor ◽  
Male Rats ◽  
Testicular Development ◽  
Insulin Like Growth Factor ◽  
Deficient Mutant ◽  
Factor I ◽  
Pubertal Growth ◽  
Body Weights ◽  
Igf I ◽  
Growth Factor I

ABSTRACT GH plays a major role in pubertal growth, effects mainly mediated by stimulation of insulin-like growth factor-I (IGF-I) production by the liver. However, the role of GH in the regulation of pubertal onset, spermatogenesis and fertility is still under debate. GH and FSH have, in addition, been implicated in the regulation of IGF-I production by Sertoli cells in a number of studies, although conflicting results have been reported. The interpretation of studies using GH-deficient mutant mice has been complicated by the presence of additional defects in the hypothalamic-pituitary-gonadal axis of these animals. We have therefore used GH-deficient mutant male rats with no other documented hormonal deficiencies to study the effect of GH administration on somatic and testicular development, circulating and testicular IGF-I concentrations and testicular histology. Body weights in GH-deficient rats substituted with GH were not significantly different from untreated or GH-treated normal rats and were significantly higher than body weights in untreated dwarf rats. Similarly, circulating IGF-I concentrations in GH-treated GH-deficient rats were not significantly different from those in untreated or GH-treated normal rats but were significantly higher than circulating IGF-I concentrations in untreated dwarf rats. No differences in testicular IGF-I concentrations were observed in any of the groups studied. Testicular weights remained low in both untreated and GH-treated GH-deficient animals compared with control animals but spermatogenesis was qualitatively and quantitatively normal in all groups at the end of the observation period. We conclude that GH does not play a major role in the regulation of testicular IGF-I production at puberty although we cannot exclude the possibility that the low but detectable levels of GH in the blood of mutant rats is sufficient to augment testicular responsiveness to gonadotrophins and therefore result in normal gonadal development. Journal of Endocrinology (1991) 131, 279–285

scholarly journals One Year of Insulin-Like Growth Factor I Treatment Does Not Affect Bone Density, Body Composition, or Psychological Measures in Postmenopausal Women1

2001 ◽  
Vol 86 (4) ◽  
pp. 1496-1503 ◽  
Author(s):  
Anne L. Friedlander ◽  
Gail E. Butterfield ◽  
Sharon Moynihan ◽  
Jeanine Grillo ◽  
Margaret Pollack ◽  
...  
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Bone Density ◽  
Density Lipoprotein ◽  
Insulin Like Growth Factor ◽  
Psychological Measures ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Turnover Markers

The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 ± 2.0 yr, 71.8 ± 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 μg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 ± 11.9 ng/mL) at 6 months (330.0 ± 52.8) and 12 months (297.7 ± 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

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