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Journal Article 2012; 33(2): 191-195 PubMed PMID: 22592200 Citation  Keywords:  Animals, Ghrelin:administration & dosage, Half-Life, Injections, Intravenous, Iodine Radioisotopes, Male, Rats, Rats, Wistar, Tissue Distribution,.   

OBJECTIVES: Ghrelin presents a multiplicity of biological functions, what is consistent with widespread expression of this peptide and its receptors. Ghrelin may act locally, but it may also influence distant cells. The aim of the study was to assess plasma activity of exogenous ghrelin and its distribution in rats.

DESIGN: Plasma radioactivity of (125)I-ghrelin (cpm) was analyzed in blood specimens collected after (125)I-ghrelin administration. Tissue uptake of (125)I-ghrelin (cpm/mg) was evaluated in 27 tissues obtained during an autopsy performed 1, 2 and four hours after (125)I-ghrelin administration. The radioactivity of the tissue specimen (cpm) was divided by the weight of the specimen (mg).

RESULTS: Plasma (125)I-ghrelin radioactivity decreased rapidly after peptide administration. The half-life time of (125)I-ghrelin was 15-18 minutes. The analysis of (125)I-ghrelin distribution revealed three profiles of its tissue uptake. The first profile was characterized by decreasing radioactivity (e.g. brain, kidney, liver). Increasing tissue radioactivity followed by a gradual decrease (second profile) was observed for example in stomach, intestine and thyroid. The third profile was described as a relatively stable radioactivity (e.g. lung, myocardium). Despite of Lugol's solution administration, thyroid uptake of (125)I-ghrelin was notably higher than in other tissues (second and third profile).

CONCLUSIONS: Exogenous ghrelin uptake in tissues that produce this peptide suggests, that ghrelin influences the biology and function of these cells also in endocrine way. Similarly, the accumulation of peptide observed in the third profile (e.g. thyroid) may reflect a potential role of ghrelin in these organs....

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Journal Article 2011; 32(5): 716-721 PubMed PMID: 22167137 Citation  Keywords:  Adiponectin:blood, Aged, Brain Ischemia:epidemiology, Female, Ghrelin:blood, Humans, Intracranial Arteriosclerosis:epidemiology, Intracranial Embolism:epidemiology, Leptin:blood, Male, Middle Aged, Risk Factors, Sex Distribution, Stroke:epidemiology, Stro.   

OBJECTIVES: Fat tissue is an important endocrine organ that produces a number of hormones and cytokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1, Tumour necrosis factor TNF α) with essential roles in regulation of many physiological functions.

METHODS: We targeted implications of adipokines in ischemic stroke patients. Patients with acute stroke were examined (n=145) and the results were compared with the control group (n=68). We have examined potential associations between leptin, adiponectin and ghrelin, and different types of stroke and traditional risk factors.

RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group. The level of leptin in women with stroke was three-times higher than in men, and the leptin levels positively correlated with obesity in both sexes. Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke. Adiponectin levels were not different between men and women with acute stroke, and correlated with atherothrombotic and lacunar stroke types in men.

CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced. More research is required to confirm our results....

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Journal Article 2011; 32(4): 437-441 PubMed PMID: 21876505 Citation  Keywords:  Adiponectin:blood, Adult, Aged, Deep Brain Stimulation:methods, Eating:physiology, Female, Ghrelin:blood, Hormones:blood, Humans, Hydrocortisone:blood, Hypothalamus:physiology, Insulin:blood, Leptin:blood, Male, Middle Aged, Parkinson Disease:metabolism, .   

OBJECTIVES: Weight gain has been reported in patients with Parkinson's disease (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To evaluate the influence of STN-DBS on weight changes, we studied food-related hormones.

DESIGN: Anthropometric parameters and food-related hormones (leptin, adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating hormone) were measured in 27 patients with STN-DBS during a 12 month period following electrode implantation.

RESULTS: Besides marked motor improvements on STN-DBS, PD patients significantly gained weight. The mean weight gain at 12 months was 5.2±(SD)5.8 kg. A significant decrease in cortisol levels compared to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected), with no significant changes in other hormones tested.

CONCLUSIONS: Changes in peripheral food-related hormones do not appear to cause weight gain in PD patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide balance remain hypothetical and necessitate further elucidation....

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Journal Article 2010; 31(3): 406-412 PubMed PMID: 20588248 Citation  Keywords:  Animals, Body Weight:drug effects, Eating:drug effects, Ghrelin:metabolism, Male, Shrews:anatomy & histology, Stomach:anatomy & histology,.   

OBJECTIVE: To investigate the distribution of ghrelin, an important appetite regulatory factor related to obesity, in the stomach of Suncus murinus, and attempted to elucidate the ghrelin-mediated regulatory effect in this animal.

METHODS: The stomachs of Suncus murinus were divided into 5 sections, cardia, fundus, greater curvature, lesser curvature, and pylorus, for investigating the ghrelin-producing cells by immunohistochemistry and Western blotting. Then Suncus murinus were randomized into two groups with ghrelin intraperitoneal injection (ghrelin-ip group) and saline intraperitoneal injection (control group), respectively. The effects of food intake and body weight were measured, and furthermore, the distribution of ghrelin in stomach was also investigated by immunohistochemistry and Western blotting.

RESULTS: The immunolocalization and protein levels of ghrelin differed significantly in different regions of the stomach of Suncus murinus. Furthermore, ghrelin administration did not change the rate of food intake, but resulted in an increase in body weight compared with the control group. In this study, we elucidated the distribution of ghrelin-producing cells in the stomach of Suncus murinus in detail for the first time. Ghrelin intraperitoneal administration was found to induce an increase in body weight without changing food intake in this species.

CONCLUSION: Our study implied ghrelin showed a different regulatory function in Suncus murinus from other species. It is considered that ghrelin may be associated with obesity-resistance phenomenon in Suncus murinus....

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Comparative Study 2010; 31(1): 147-154 PubMed PMID: 20150876 Citation  Keywords:  Acromegaly:etiology, Adenoma:complications, Adult, Female, GTP-Binding Protein alpha Subunits:genetics, Ghrelin:genetics, Growth Hormone-Secreting Pituitary Adenoma:complications, Humans, Male, Middle Aged, Mutation, RNA, Messenger:metabolism, Receptors, .   

OBJECTIVE: The purpose of this study was to investigate the relationship between the ghrelin or GHSR-1a mRNA levels and clinical characteristics and to confirm the effect of gsp mutations on ghrelin/GHSR-1a system in human GH-secreting pituitary adenomas.

METHODS: The expression levels of ghrelin, GHSR-1a mRNA were determined by SYBR green real-time fluorescent quantitative PCR. The gsp mutations in 43 cases of human GH-secreting pituitary adenomas were detected using PCR-DNA direct sequencing analysis. Clinical data were obtained from the medical records of 43 acromegalic patients who had GH and IGF-1 assays in the same laboratory.

RESULTS: The expression of GHSR-1a correlated positvely with tumor size (R=0.411, p=0.006) and invasiveness (p<0.05). In contrast, ghrelin mRNA levels correlated positively only with tumor size (R=0.331, p=0.030) but not with tumor invasiveness (p>0.05). The expression level of GHSR-1a mRNA was significantly higher in gsp positive adenomas than in negative adenomas (p<0.05). Whereas, there was no significant difference in the expression of ghrelin mRNA between gsp mutation-positive and -negative adenomas (p>0.05). Additionally there was a significant positve correlation between the ghrelin and GHSR-1a mRNA expression levels in gsp-positive (R=0.553, p=0.040) or -negative adenomas (R=0.489, p=0.007).

CONCLUSIONS: GHSR-1a correlated positively with tumor size and invasiveness, while ghrelin correlated positively only with tumor size. Gsp mutations may upregulate the expression of GHSR-1a mRNA and have no effect on ghrelin mRNA levels in human GH-secreting pituitary adenomas....

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Journal Article 2009; 30(2): 245-255 PubMed PMID: 19675514 Citation  Keywords:  Acromegaly:blood, Acylation, Adult, Aged, Blood Glucose:metabolism, Cholesterol:blood, Female, Ghrelin:blood, Growth Hormone:blood, Humans, Hypercholesterolemia:blood, Hyperglycemia:blood, Hyperinsulinism:blood, Insulin:blood, Insulin-Like Growth Factor I.   

UNLABELLED: It is unknown if altered ghrelin secretion might contribute to the development of metabolic complications in acromegaly. The AIM OF THE STUDY was to: 1) assess if serum concentrations of total and acylated ghrelin in patients with acromegaly differ in the presence of various metabolic complications (hypercholesterolemia, hyperinsulinemia, hyperglicemia). 2) assess the correlations between concentrations of ghrelin and concentrations of GH, IGF-1, cholesterol, insulin and glucose in patients with acromegaly.

MATERIALS: 24 patients with previously diagnosed acromegaly (11 subjects with active and 13 subjects with inactive disease) and 12 healthy subjects. 23 subjects were treated in the past with neurosurgery, 3 subjects with radiotherapy. 7 patients were receiving octreotide LAR at the time of the study.

METHODS: In all studied subjects the concentrations of total ghrelin, acylated ghrelin, GH, IGF-1, insulin, glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglicerydes, were measured.

RESULTS: The concentrations of total and acylated ghrelin did not significantly differ between patients with active and inactive disease. The mean concentrations of total and acylated ghrelin were significantly higher in acromegalic patients who presented with hypercholesterolemia compared with patients with normocholesterolemia. In patients with hypercholesterolemia the ratio of acylated/total ghrelin was 16%. In patients with active acromegaly there was a statistically significant positive correlation between the concentration of total ghrelin and the concentration of total cholesterol and LDL cholesterol. There was also a positive correlation between the concentration of acylated ghrelin and LDL cholesterol (without statistical significance). In patients with inactive acromegaly there was a statistically significant positive correlation between the concentration of acylated ghrelin and the concentration of triglycerides and a positive correlation between total ghrelin and triglycerides, but statistically insignificant. There were no differences in ghrelin levels depending on the insulin and glucose concentrations.

CONCLUSIONS: Some metabolic complications of the disease might result not only from GH hypersecretion but also from altered ghrelin secretion....

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Comparative Study 2008; 29(6): 929-938 PubMed PMID: 19112387 Citation  Keywords:  Adenoma:classification, Gene Expression Regulation, Neoplastic:physiology, Ghrelin:genetics, Humans, Immunohistochemistry, Pituitary Neoplasms:classification, RNA, Messenger:analysis, Somatotrophs:metabolism,.   

OBJECTIVES: It has been suggested that ghrelin synthesized locally in pituitary regulates the function and growth of pituitary cells in autocrine/paracrine way and might be an important factor of pituitary tumorogenesis. The expression of ghrelin receptor in neoplastic cells of pituitary adenomas has also been demonstrated. In vitro studies confirmed that ghrelin stimulates the proliferation of somatotroph cells in GH3 cell line. The presence of both ghrelin mRNA and protein was detected in a number of benign and malignant neoplasms as well as in neoplastic cells of the tissues which do not express ghrelin in physiological conditions. This study showed the presence of ghrelin mRNA and its protein in different types of pituitary adenomas.

DESIGN: The samples of 37 pituitary adenomas were obtained during standard neurosurgical tumor removal. The study tissues included 20 somatotroph tumors (15 patients treated and 5 patients untreated with octreotide LAR before the surgery), 12 nonfunctioning adenomas, 4 prolactinomas and 1 ACTH-secreting tumor. The control included samples of normal mucous membrane of the stomach and normal pituitaries. Expression of ghrelin mRNA was studied in 28 pituitary adenomas by RT-PCR. Immunohistochemical evaluation of ghrelin presence was performed in 34 tumors.

RESULTS: The presence of ghrelin gene transcripts was demonstrated in 10 out of 15 examined somatotroph tumors (obtained from patients treated with octreotide LAR before the surgery) and also in 2 out of 4 samples of prolactinomas, 7 out of 8 of nonfunctioning tumors and in 2 samples of normal pituitary. Immunohistochemical analyses revealed the presence of the protein in all 5 examined somatotroph tumors obtained from patients not treated prior to the surgery and in 10 out of 15 tumors obtained from patients treated with octreotide LAR. The peptide was detected also in 10 out of 12 examined nonfunctioning tumors and in 2 examined PRL-secreting tumors. The immunostaining for ghrelin was not shown in normal pituitaries.

CONCLUSIONS: The study demonstrated that ghrelin gene is expressed in somatotroph adenomas, both treated and untreated with octreotide LAR before the surgery, and also in other types of pituitary adenomas (prolactinomas and nonfunctioning adenomas)....

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Clinical Trial 2008; 29(1): 100-106 PubMed PMID: 18283260 Citation  Keywords:  Adolescent, Adult, Aged, Aging:blood, Blood Glucose:metabolism, Body Weight:physiology, Dehydroepiandrosterone Sulfate:blood, Estradiol:blood, Ghrelin:blood, Growth Hormone:blood, Humans, Insulin:blood, Insulin-Like Growth Factor I:metabolism, Leptin:bloo.   

OBJECTIVES: Ghrelin, a natural ligand of the growth-hormone secretagouges receptor is the peptide known because of its growth hormone (GH)-releasing as well as orexigenic actions. THE AIM of the study was to examine the relationship between ghrelin levels and age, weight, glucose metabolism markers, GH, IGF-1 and androgens in men.

PATIENTS AND METHODS: The study included 19 healthy men aged 16-73 yrs, mean 46,8 +/-18,5 (mean +/- SD). The height, weight, and body mass index (BMI) of the study subjects were assessed and serum concentration of fasting ghrelin, leptin, GH, IGF-1, glucose, insulin, estradiol, testosterone and DHA-S were measured.

RESULTS: The negative correlation between age and serum ghrelin levels (r=-0,52; p<0,04) in men was found. In men under 30 years old serum ghrelin levels were significantly higher compared to men over 60 years old (p<0,02). Serum ghrelin levels in men were significantly lower compared to healthy women aged 43,5 +/- 12 years old (p<0,008). Serum insulin levels correlated negatively with ghrelin levels (r= -0,87; p<0,0006) and serum testosterone concentrations correlated with ghrelin levels (r= 0,69; p<0,00006).

CONCLUSION: Our findings demonstrate that the serum ghrelin levels in men decline with age, is lower than in women and correlate negatively with fasting insulin levels. We demonstrated, for the first time, that serum testosterone levels in men correlate with total ghrelin levels....

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