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.
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ABSTRACT: We aimed to evaluate the ghrelin levels in the children with adenoid or tonsil hyperthrophies. The study included 27 children (17 boys and 10 girls). Mean age was 6.9+/-3.5 years, ranging from 3 to 16. Ghrelin levels in the patients and their weight and height measurements were evaluated before surgery and after 3 months later of the operation. While 18 (67%) children were operated for adenoid hypertrophy, 9 (33%) children were operated for adenoid and tonsil hypertrophy. It was found that postoperative ghrelin levels were significantly decreased whereas weight and BMI scores were significantly increased (p<0.01). A weak correlation was observed between preoperative ghrelin and weight (r=-0.29). This negative correlation became more profound at the postoperative 3rd month examination (r=0.85) (p<0.01). The present study showed that the surgical treatment provides positive contributions on the growing of children with adenoid and tonsil hypertrophies. The ghrelin levels were significantly decreased at the postoperative period in the children, and a negative relationship was observed between the ghrelin levels and the weight. These findings suggest that blood ghrelin levels may be useful as a parameter for following the development of the children.International journal of pediatric otorhinolaryngology 03/2009; 73(5):685-7. · 0.85 Impact Factor
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ABSTRACT: Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin's cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin. Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.Journal of Endocrinology 02/2006; 188(1):37-47. · 4.06 Impact Factor
- Journal of Bone and Mineral Research 10/2005; 20(9):1497-506. · 6.13 Impact Factor