Hexarelin, a growth hormone - releasing peptide, counteracts bone loss in gonadectomized male rats.
ABSTRACT The age-related decline in growth hormone (GH) secretion has been implicated in the pathogenesis of involutional bone loss. Whether restoration of GH secretion might be helpful in maintaining and/or improving bone mass during aging is still unsettled. The aim of the present study was to examine the effects of 30-day treatment with hexarelin (HEXA, 50 microg/kg subcutaneously b.i.d.), a highly effective GH-releasing compound, on bone metabolism and bone mineral density (BMD) in intact and osteopenic gonadectomized (GDX) mature male rats. Serum total alkaline phosphatase (ALP, bone formation marker) and bone resorption markers (lysylpyridinoline, LP and hydroxylysylpyridinoline, HP) were measured before and 7, 14 and 30 days after treatment. BMD was measured by dual-energy X-ray absorptiometry at lumbar vertebrae, femoral metaphysis and diaphysis before and at the end of the experiment. In intact rats, HEXA significantly (P<0.05) decreased LP (-36.3%) and HP (-22.8%) excretion at day 7, whereas it did not change serum ALP activity and BMDs. In GDX rats, HEXA completely prevented the significant (P<0. 01) increase in urinary excretion of both LP (+143.8%) and HP (+119. 4%), the early decrease in ALP activity (-26.5%) and the significant (P<0.05) decrease in BMDs in the femoral metaphysis (-7.9%) and lumbar vertebrae (-6.8%) caused by androgen deficiency. The bone-protective effects of HEXA could be attributed, at least in part, to its GH-releasing activity since chronic-treated rats maintained the GH response to an acute challenge with HEXA. The evidence that HEXA, unlike GH, inhibits bone resorption indicates that other mechanisms contribute to the bone sparing effect of HEXA.
Article: Growth hormone secretagogues[Show abstract] [Hide abstract]
ABSTRACT: Growth hormone secretagogues (GHSs) are synthetically produced peptides and non-peptides that stimulate growth hormone (GH) release by acting on one or more specific receptors. Treatment with GH itself is established in GH deficient children and adults and may also be useful in frail, elderly adults, in abdominally/viscerally obese subjects, in patients with congestive heart failure and in patients suffering from nitrogen-wasting catabolic disease. In these conditions, the newly developed class of orally-active GHSs may be attractive alternatives to sc. GH injections. This review focuses on recently patented GHSs and their claimed indications, however, other GHSs and their possible uses have also been included.IDrugs: the investigational drugs journal 02/2005; 10(7):1071-1080. · 2.33 Impact Factor
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ABSTRACT: Increasing evidence suggests a role for oxidative stress in age-related decrease in osteoblast number and function leading to the development of osteoporosis. This study was undertaken to investigate whether ghrelin, previously reported to stimulate osteoblast proliferation, counteracts tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in MC3T3-E1 osteoblastic cells as well as to characterize the ghrelin receptor (GHS-R) involved in such activity. Pretreatment with ghrelin (10(-7)-10(-11 )M) significantly increased viability and reduced apoptosis of MC3T3-E1 cells cultured with t-BHP (250 μM) for three hours at the low concentration of 10(-9 )M as shown by MTT assay and Hoechst-33258 staining. Furthermore, ghrelin prevented t-BHP-induced osteoblastic dysfunction and changes in the cytoskeleton organization evidenced by the staining of the actin fibers with Phalloidin-FITC by reducing reactive oxygen species generation. The GHS-R type 1a agonist, EP1572 (10(-7)-10(-11 )M), had no effect against t-BHP-induced cytotoxicity and pretreatment with the selective GHS-R1a antagonist, D-Lys(3)-GHRP-6 (10(-7 )M), failed to remove ghrelin (10(-9) M)-protective effects against oxidative injury, indicating that GHS-R1a is not involved in such ghrelin activity. Accordingly, unacylated ghrelin (DAG), not binding GHS-R1a, displays the same protective actions of ghrelin against t-BHP-induced cytotoxicity. Preliminary observations indicate that ghrelin increased the trimethylation of lys4 on histones H3, a known epigenetic mark activator, which may regulate the expression of some genes limiting oxidative damage. In conclusion, our data demonstrate that ghrelin and DAG promote survival of MC3T3-E1 cell exposed to t-BHP-induced oxidative damage. Such effect is independent of GHS-R1a and is likely mediated by a common ghrelin/DAG binding site.Amino Acids 04/2014; · 3.65 Impact Factor
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ABSTRACT: Moisture disposal and thermal behaviour (shoe climate) over a number of hours is an important factor in shoe comfort, besides the fit of the shoes and energy (absorption). In most of shoe-testing laboratories these properties are frequently measured on materials, like leather linings and upper- or in-soles. Data for these materials can give an indication of the performance of the shoe, although differences can occur dependent on the shoe construction and the production methods used. At TNO, a test-method, the WSCR-method (Whole Shoe Comfort Rating), is set up where both the water vapour transport and thermal characteristics of complete shoes can be measured with the aid of an artificial foot. The method uses a flexible sock that is impermeable to water, but permeable to water vapour. This sock is placed into the shoe specimen, which is filled with water at a controlled temperature. The whole set-up is placed upon a balance (connected to a computer), in a laboratory (20°C and 65% relative humidity) or in a climatic chamber or box. The air speed is maintained at approximately 1 m/s. The Water Vapour Absorption, Water Vapour Permeability and Water Vapour Transport (WVT) are calculated from the measurements, as well as the average heat conductivity of the whole shoe.Five different trekking shoes were compared for (thermal) comfort. The results show that the shoe with the highest WVT-value have a 35% higher value than the shoe with the lowest value. For heat resistance, the same type of shoe had a 30% higher value than the lowest. The heat resistance and WVT values showed a significant negative correlation (−0.97; p<0.01). It can be concluded that the trekking shoes have a worse performance with regard to comfort compared to the other shoes, but in terms of functionality the trekking shoes were better than the other shoes. The present study shows the importance of different comfort aspects (e.g. climate, fit, shock absorption) and should lead to a whole shoe comfort model that will help in evaluating the comfort of shoes in an objective manner.Elsevier Ergonomics Book Series.