Local administration of growth hormone stimulates tendon collagen synthesis in elderly men

2012 ◽  
Vol 113 (9) ◽  
pp. 1432-1438 ◽  
Author(s):  
Poul Vestergaard ◽  
Jens Otto Lunde Jørgensen ◽  
Jens L. Olesen ◽  
Ermina Bosnjak ◽  
Lars Holm ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Collagen Synthesis ◽  
Synthesis Rate ◽  
Saline Control ◽  
Type I ◽  
Elderly Men ◽  
Healthy Elderly ◽  
Igf I ◽  
Local Injections ◽  
Tendon Collagen

Tendon collagen content and circulating growth hormone (GH) are reduced in elderly. In a placebo-controlled, double-blinded study, we examined if local injections of rhGH enhance collagen synthesis in healthy elderly men (61 ± 1 yr). Two injections of rhGH or saline (control) were injected into each of the patient's patellar tendons, respectively. Subsequently, tendon collagen fractional synthesis rate (FSR) and an indirect marker of type I collagen synthesis (PINP) were measured. Within the first 6 h after the last injections, a tendency towards a higher tendon collagen FSR was observed in 10 out of 12 subjects ( P = 0.08). Similarly, PINP was higher 3–4 h after the last GH injection ( P = 0.05). Serum IGF-I did not change from baseline, whereas peritendinous bioactive IGF-I was higher in the GH leg vs. control ( P = 0.05). In conclusion, local injections of rhGH increase tendon collagen synthesis in humans, either directly or indirectly by increasing local bioactive IGF-I.

Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women

2009 ◽  
Vol 106 (4) ◽  
pp. 1385-1393 ◽  
Author(s):  
Mette Hansen ◽  
Mads Kongsgaard ◽  
Lars Holm ◽  
Dorthe Skovgaard ◽  
S. Peter Magnusson ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Postmenopausal Women ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Volume Fraction ◽  
Structural Characteristics ◽  
Biomechanical Properties ◽  
Synthesis Rate ◽  
Type I ◽  
Tendon Collagen

The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH2-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users ( P < 0.001), whereas no group difference was seen in tendon NH2-terminal propeptide of type I collagen synthesis ( P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users ( P < 0.05), whereas the percentage of large fibrils tended to be greater in control ( P = 0.10). A lower Young's modulus (GPa/%) was found in ERT users ( P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.

Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men

1991 ◽  
Vol 124 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Hiroshi Bando ◽  
Chenyu Zhang ◽  
Yukinobu Takada ◽  
Ryuichi Yamasaki ◽  
Shiro Saito
Keyword(s):  
Growth Hormone ◽  
Young Men ◽  
The Elderly ◽  
Elderly Group ◽  
Elderly Men ◽  
Age Related ◽  
Igf I ◽  
Basal Plasma ◽  
Plasma Gh ◽  
Ghrh Test

Abstract. The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p<0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0±2.7 vs 20.3±1.8 ng · h−1 · 1−1 (p<0.001), and 21.8±4.6 vs 5.4±1.1 μg · h−1 · 1 (p<0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.

scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P &lt; 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.

Effects of single nightly injections of growth hormone—releasing hormone (GHRH 1–29) in healthy elderly men

Metabolism ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Janet Vittone ◽  
Marc R. Blackman ◽  
Jan Busby-Whitehead ◽  
Chris Tsiao ◽  
Kerry J. Stewart ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Releasing Hormone ◽  
Elderly Men ◽  
Releasing Hormone ◽  
Healthy Elderly

scholarly journals Insulin-like growth factor I and insulin-like growth factor binding protein 5 in Crohn's disease

2001 ◽  
Vol 280 (5) ◽  
pp. G1022-G1029 ◽  
Author(s):  
E. M. Zimmermann ◽  
L. Li ◽  
Y. T. Hou ◽  
N. K. Mohapatra ◽  
J. B. Pucilowska
Keyword(s):  
Smooth Muscle ◽  
Crohn’S Disease ◽  
Growth Factor ◽  
Crohn's Disease ◽  
Collagen Synthesis ◽  
Binding Protein ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Muscularis Externa

Insulin-like growth factor (IGF)-I and its binding protein IGF binding protein 5 (IGFBP-5) were highly expressed in inflamed and fibrotic intestine in experimental Crohn's disease. IGF-I induced proliferation and increased collagen synthesis by smooth muscle cells and fibroblasts/myofibroblasts in vitro. Here we studied IGF-I and IGFBP-5 in Crohn's disease tissue. Tissue was collected from patients undergoing intestinal resection for Crohn's disease. IGF-I and IGFBP-5 mRNAs were quantitated by RNase protection assay and Northern blot analysis, respectively. In situ hybridization was performed to localize mRNA expression, and Western immunoblot was performed to quantitate protein expression. IGF-I and IGFBP-5 mRNAs were increased in inflamed/fibrotic intestine compared with normal-appearing intestine. IGF-I mRNA was expressed in multiple cell types in the lamina propria and fibroblast-like cells of the submucosa and muscularis externa. IGFBP-5 mRNA was highly expressed in smooth muscle of the muscularis mucosae and muscularis externa as well as fibroblast-like cells throughout the bowel wall. Tissue IGFBP-5 protein correlated with collagen type I ( r = 0.82). These findings are consistent with a mechanism whereby IGF-I acts on smooth muscle and fibroblasts/myofibroblasts to increase collagen synthesis and cellular proliferation; its effects may be modulated by locally expressed IGFBP-5.

scholarly journals Tendon collagen synthesis at rest and after exercise in women

2007 ◽  
Vol 102 (2) ◽  
pp. 541-546 ◽  
Author(s):  
Benjamin F. Miller ◽  
Mette Hansen ◽  
Jens L. Olesen ◽  
Peter Schwarz ◽  
John A. Babraj ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Collagen Synthesis ◽  
Synthesis Rate ◽  
Menstrual Phase ◽  
Late Luteal Phase ◽  
Significant Difference ◽  
Healthy Female ◽  
Early Follicular Phase ◽  
Fractional Synthesis ◽  
Tendon Collagen

In general, there is a higher incidence of musculoskeletal injuries during physical activity in women than in men. We hypothesized that in women rates of tendon collagen synthesis would be lower than in men at rest and after exercise, especially in the later luteal phase when estrogen and progesterone concentrations are higher than the early follicular phase. We studied tendon collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in either the early follicular ( n = 8) or the late luteal phase ( n = 7) 72 h after an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72 h) and compared the results with those previously obtained for men. Samples were taken from the patellar tendon in both the exercised and rested legs to determine collagen FSR by the incorporation of [15N]proline into tendon collagen hydroxyproline. There was no effect of menstrual phase on tendon collagen synthesis either at rest or after exercise. However, there was a significant difference between women and men at rest (women = 0.025 ± 0.002%/h, men = 0.045 ± 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 ± 0.005%/h; men = 0.058 ± 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were not different in women, whereas in men tendon collagen synthesis remained significantly elevated 72 h after exercise. It is concluded that both in the resting state and after exercise, tendon collagen FSR is lower in women than in men, which may contribute to a lower rate of tissue repair after exercise.

Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans

2011 ◽  
Vol 110 (1) ◽  
pp. 137-141 ◽  
Author(s):  
Britt Christensen ◽  
Sune Dandanell ◽  
Michael Kjaer ◽  
Henning Langberg
Keyword(s):  
Placebo Group ◽  
Collagen Synthesis ◽  
Prolonged Exercise ◽  
Inflammatory Diseases ◽  
Type I ◽  
Collagen Turnover ◽  
Tendon Tissue ◽  
Patella Tendon ◽  
Exercise Induced ◽  
Tendon Collagen

NSAIDs are widely used in the treatment of inflammatory diseases as well as of tendon diseases associated with pain in sports and labor. However, the effect of NSAID intake, and thus blockade of PGE2 production, on the tendon tissue adaptation is unknown. The purpose of the present study was to elucidate the possible effects of NSAID intake on healthy tendon collagen turnover in relation to a strenuous bout of endurance exercise. Fifteen healthy young men were randomly assigned into two experimental groups, with one group receiving indomethacin (oral 2 × 100 mg Confortid daily for 7 days; NSAID; n = 7) and a placebo group ( n = 8). Both groups were exposed to a prolonged bout of running (36 km). The collagen synthesis NH2-terminal propeptide of type I (PINP) and PGE2 concentrations were measured before and 72 h following the run in the patella tendon by microdialysis. The peritendinous concentrations of PINP increased significantly in the placebo group as a result of the run, as shown previously. PGE2 levels were significantly decreased 72 h after the run compared with basal levels in the subjects treated with NSAID and unchanged in the placebo group. The NSAID intake abolished the adaptive increase in collagen synthesis in the patella tendon found in the placebo group in response to the prolonged exercise ( P < 0.05). The present study demonstrates that intake of NSAID decreased interstitial PGE2 and abolished the exercise-induced adaptive increase in collagen synthesis in human tendons.

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