Effect of Glucocorticoid-, Parathyroid- and Thyroid Hormones Excess on Human Iliac Crest Bone Matrix Insulin-like Growth Factor (IGF)-I in Patients with Osteoporosis

2009 ◽  
Vol 118 (05) ◽  
pp. 310-314
Author(s):  
C. E. Pepene ◽  
T. Seck ◽  
I. Diel ◽  
H. W. Minne ◽  
R. Ziegler ◽  
...  
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19671-19671
Author(s):  
T. Takahata ◽  
M. Munakata ◽  
Y. Sakata ◽  
K. Nakagawa ◽  
T. Mukaiyama ◽  
...  

19671 Background: Pituitary and thyroid hormones are known to be altered in anorexia nervosa, but few hormonal studies have been performed in cancer anorexia-cachexia syndrome. This study focused on growth hormone (GH) and Insulin-like Growth Factor (IGF)-I axis in cancer patients. Methods: To investigate the relationship among performance status (PS), nutritional and hormonal status, blood sampling was performed to measure GH, IGF-I, IGF-binding protein 3(IGFBP-3), T3, T4, complete blood counts and blood chemistry profiles for 15 cancer patients in each of PS0–1, PS2, PS3 and PS4 after the informed consent was obtained. Results: A total of 58 patients were evaluated including 15 patients in PS0–1, PS2 and PS3 and 13 in PS4. Hemoglobin and albumin levels went down along with progression of PS. GH level was high and T3 was low in poor PS. T4 and IGFBP-3 were lower in PS4 than those of other PS. There is a tendency of low IGF-I and thyroid hormones and high GH levels in poor PS as compared with those of good PS (p=0.0064 for IGF-I, p<0.001 for T3, and T4, not significant for GH analyzed by ANOVA). Conclusions: Abnormal GH - IGF-I axis was more pronounced in poor PS. It is conceivable that normalization of this abnormality can improve cancer anorexia-cachexia syndrome and new drug development for such normalizing agents is warranted. No significant financial relationships to disclose.


1995 ◽  
Vol 146 (2) ◽  
pp. 239-245 ◽  
Author(s):  
J M Brameld ◽  
P A Weller ◽  
J C Saunders ◽  
P J Buttery ◽  
R S Gilmour

Abstract The effects of various hormones commonly added to hepatocyte culture media upon the expression of the GH receptor (GHR) and insulin-like growth factor-I (IGF-I) genes in cultured porcine hepatocytes were investigated. Preliminary investigations indicated that there was an absolute requirement only for insulin, with high losses of cell viability upon long term exclusion of insulin from the culture medium. The decline in GHR expression with time in culture was found to be less when high levels of glucose were included in the medium. Therefore the basal culture medium used in these studies was Williams' medium E supplemented with 0·2% (w/v) BSA, 5000 mg glucose/l and 100 nmol porcine insulin/l. The addition of dexamethasone (100 nmol/l) increased the expression of both GHR and IGF-I (class 1 transcripts only) mRNA (P<0·001 and P<0·05 respectively), and resulted in an increased responsiveness of IGF-I mRNA expression to GH (1 μg/ml), when the two were added in combination (although only class 1 transcripts were shown to be statistically significant, P<0·01). The addition of either thyroid hormone (1 nmol/l T3 or T4) alone also increased the expression of GHR mRNA (P<0·01) in addition to the dexamethasone stimulated expression, with T4 appearing to decrease IGF-I expression slightly (P<0·05) (either on its own or with T3). As with dexamethasone, the thyroid hormones increased the response of IGF-I mRNA expression to GH (1 μg/ml) when added in combination with GH (P<0·001). These observations demonstrate one possible mechanism for the interactions of glucocorticoids and thyroid hormones with the GH–IGF axis. Journal of Endocrinology (1995) 146, 239–245


2004 ◽  
pp. 81-91 ◽  
Author(s):  
CE Pepene ◽  
T Seck ◽  
I Diel ◽  
HW Minne ◽  
R Ziegler ◽  
...  

OBJECTIVE: Data from cell culture experiments suggest that local growth factors (GFs) may mediate the effects of estrogens, calcitonin or fluor ions on the skeleton. To assess the in vivo relevance of the in vitro reports, the effect of fluor salts, hormone replacement therapy (HRT) and calcitonin on the concentrations of IGF-I, IGF-II and transforming growth factor (TGF)-beta 1 in bone matrix extracts from osteoporotic patients was evaluated. DESIGN: Iliac crest bone biopsies were obtained from 170 patients (76 men and 94 women) with primary osteoporosis aged 55.5+/-0.8 Years. METHODS: Bone matrix extraction was performed based on a guanidine-HCl/ethylendiamine-tetra-acetic acid method. RESULTS: In comparison with age- and body mass index (BMI)-matched controls, no influence of long-term therapy with fluor ions (n=41) or calcitonin (n=16) on the bone matrix concentration of GFs was noticed. Postmenopausal women with osteoporosis on HRT (n=39) had lower skeletal IGF-I but not IGF-II levels as compared with age- and BMI-matched non-users. However, the lower rate of bone turnover in women with HRT may account for this difference, since the significance was lost after adjustment for alkaline phosphatase. Likewise, a tendency for lower TGF-beta 1 levels was observed in HRT users as compared with non-users but was lost after adjustment for bone turnover. None of the therapies influenced the serum levels of GFs when patients receiving continuous therapy for at least 1 Year before bone biopsy were considered. CONCLUSIONS: Our data suggest no direct effect of fluor therapy on skeletal GFs levels. At the concentrations used, neither HRT nor calcitonin appeared to exert any significant influence on serum or bone matrix GF levels.


1998 ◽  
Vol 83 (7) ◽  
pp. 2331-2337 ◽  
Author(s):  
Thomas Seck ◽  
Beate Scheppach ◽  
Stefan Scharla ◽  
Ingo Diel ◽  
Werner F. Blum ◽  
...  

Insulin-like growth factor-I (IGF-I) and -II are important local regulators of bone metabolism, but their role as determinants of human bone mass is still unclear. In the present study, we analyzed the concentration of IGF-I and -II in the bone matrix of 533 human biopsies from the iliac crest that were obtained during surgery for early breast cancer. There was an inverse association of bone matrix IGF-I concentration with age that was unaffected by menopause. Bone matrix IGF-I was positively associated with histomorphometric and biochemical parameters of bone formation and bone resorption and with cancellous bone volume. Based on the estimates of the linear regression analysis, women with a bone matrix IGF-I concentration 2 sd above the mean had a 20% higher bone volume than women with a bone matrix IGF-I concentration 2 sd below the mean. In contrast, serum IGF-I was neither correlated with bone turnover nor with bone volume and was only weakly associated with bone matrix IGF-I when adjusted for the serum concentration of IGF binding protein-3. Bone matrix IGF-II was positively associated with the osteoblast surface, but in contrast to IGF-I, tended to be positively associated with age and was unrelated to cancellous bone volume. In summary, our study suggests the following. 1) The concentration of IGF-I in cancellous bone undergoes age-related decreases that are similar to those of circulating IGF-I. 2) Menopause has no effect on this age-related decline. 3) Physiological differences in bone matrix IGF-I are associated with differences in iliac crest cancellous bone volume. 4) Bone matrix IGF-I is a better predictor of cancellous bone volume than circulating IGF-I. 5) The role of IGF-II in human bone tissue is clearly distinct from that of IGF-I.


2000 ◽  
Vol 80 (2) ◽  
pp. 329-335 ◽  
Author(s):  
C. Bertozzi ◽  
D. Portetelle ◽  
S. Massart ◽  
A. Prandi ◽  
V. Darras ◽  
...  

To improve carcass quality in finishing calves, some breeders use preparations containing corticoids alone or in association with other growth promoters. We have investigated the effects of dexamethasone treatment on insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP-2 and 3) and thyroid hormones (T3, T4, free T4). Limousine male calves were allocated to a control group (C) (n = 18) and a group (n = 18) that received dexamethasone esters (DEX). Blood and hepatic tissue samples were collected at slaughtering. Thyroid hormones and IGF-I plasma levels were measured by RIA and IGFBPs were evaluated by immunoblotting. Hepatic type I 5′deiodinase (5′D-I) activity was determined by enzyme assay and hepatic expression of mRNA for GH receptor, IGF-I, IGFBP-2, IGFBP-3 and type I deiodinase (D-I) was evaluated by dot blot analysis. Plasma IGF-I and IGFBP-3 levels were reduced by the DEX treatment (P < 0.001 and P < 0.01, respectively) while IGFBP-2 was unaffected. Significant plasma changes for IGF-I and IGFBP-3 were not corroborated by hepatic mRNA levels, for which only a slight non-significant decrease was noted. Growth hormone receptor mRNA expression was increased after treatment (P < 0.01). T3 plasma level was higher in DEX animals (P < 0.05) than in C calves. Finally, treatment increased 5′D-I activity in the hepatic tissue (P < 0.001) and seemed to also affect D-I mRNA expression (P = 0.1). In conclusion, dexamethasone ester injection in calves altered some of their endocrinological parameters; this could explain the catabolic action of corticoids in the bovine species. Key words: Calves, corticoids, IGF-I, IGFBPs, thyroid axis


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