The effects of growth hormone status on circulating levels of vascular growth factors.

BACKGROUND: Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin-2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology. AIM: To investigate the effect of GH status on the circulating levels of angiogenic factors. DESIGN: We measured the levels of six endothelial growth modulators, four angiogenic growth factors and two inhibitors of angiogenesis in 35 untreated acromegalics, 36 untreated GH-deficient subjects and 101 normal control subjects. Fifteen GH-deficient subjects were also studied before and 1 year after treatment with GH. RESULTS: Mean angiogenin concentrations were increased in acromegaly and decreased in GH-deficient subjects compared to control subjects. Endostatin levels showed a similar pattern although the elevated levels in acromegalic subjects did not achieve statistical significance. Angiogenin and endostatin levels both correlated significantly with IGF-I levels (R = 0.61, P < 0.001 and R = 0.22, P < 0.01, respectively). The relationship between angiogenin and IGF-I levels remained significant even after correction for gender, age, body mass index (BMI) and insulin resistance. There were no significant differences in the levels of HGF, VEGF, VEGF-C or angiopoietin-2 between the three groups. VEGF-D levels were elevated in both acromegalic and GH-deficient male subjects. A similar pattern was apparent in female subjects. After GH treatment, a significant reduction in VEGF-D levels and a significant rise in endostatin levels were observed in GH-deficient subjects. A nonsignificant increase in angiogenin levels was also observed. CONCLUSION: These data indicate that significant perturbations in the levels of vascular growth modulators are present in both acromegaly and GHD. While changes in endostatin and angiogenin levels appear to correlate with IGF-I levels, VEGF-D levels show similar perturbations in both acromegaly and GHD. Further studies are required to determine the relationship of the perturbations to endothelial dysfunction in these conditions.

Ghrelin and leptin elevation in postoperative intra-abdominal sepsis.

BACKGROUND: Both ghrelin and leptin are important signals in the regulation of food intake and energy balance. Leptin concentrations are elevated in the majority of obese individuals, and its levels usually correlate with adiposity and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective properties. Many other regulatory effects of both ghrelin and leptin involving cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New experimental studies show both hormones as new acute phase reactants in animal models of inflammatory reaction. The aim of this study was to characterize the levels of circulating ghrelin and leptin in relation to systemic inflammatory response. We used a postoperative bacterial sepsis after large abdominal surgery as a model of cytokine network hyperstimulation. PATIENTS AND METHODS: The prospective study was performed on 25 surgical patients with proven postoperative intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin (RIA), leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 (ELISA analysis), CRP and alpha1-antitrypsin (nephelometric analysis) were analyzed. RESULTS: Authors demonstrate statistically significant elevation of plasma ghrelin (492.3+/-70.6 ng/l) and leptin (31.6+/-12.2 microg/l) compared with the control group (336.5+/-46,1, p<0.01 for ghrelin, 3.5+/-1.2 microg/l, p<0.001 for leptin). The regression coefficient was the highest for ghrelin and IL-6 (r=0,44, p<0.05), and for ghrelin and TNF (r=0.43, p<0.05) in the sepsis group. In regard to leptin, the regression coefficient was the highest for IL-6 and leptin (r=0.53, p<0.05) and for leptin and CRP (r=0.51, p<0.05). There was no significant correlation between ghrelin and IL-1beta, ghrelin and sIL-2R, and leptin and IL-1beta. CONCLUSIONS: During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma levels are elevated and positively correlate with both inflammatory cytokines (TNF-alpha, IL-6) and main APP member (CRP). It supports experimental finding that TNF-alpha and IL-6 can be important regulatory factors of their synthesis. This hormonal reaction is not specific to sepsis--the significant increase of both ghrelin and leptin occurs during an uncomplicated postoperative response, although in a lesser extent than was shown in sepsis.

Plasma ghrelin levels in patients with short bowel syndrome.

Ghrelin is a novel peptide hormone which was identified as an endogenous growth hormone secretagogue. It is mainly secreted in the stomach, but important sites of its secretion are other parts of the gastrointestinal tract. Ghrelin is thought to be involved not only in regulation of growth hormone secretion but also in regulation of food intake and nutritional status. This study was aimed to investigate the changes in plasma ghrelin levels in patients with short bowel syndrome. Twenty-four patients with malnutrition due to short bowel syndrome and eleven healthy controls were included in the study. They underwent clinical examination and assessment of plasma or serum levels of ghrelin leptin, soluble leptin receptor, IGF-I, IGFBP-1 and IGFBP-3. Plasma ghrelin levels were decreased in patients with short bowel syndrome (p<0.01). Furthermore, decreased serum levels of IGF-I (p<0.01) and IGFBP-3 (p<0.001) were found in patients with short bowel syndrome. Other laboratory differences between both groups were not significant. No relationship between ghrelin and other determined variables was found. We conclude that plasma ghrelin levels are decreased in the group of patients with short bowel syndrome. It is probably because of a decrease in the tissue mass that is able to secrete ghrelin.