Role Of Ghrelin Research Articles

The role of ghrelin in weight-regulation disorders: implications in clinical practice.

Ghrelin, an orexigenic protein with a unique lipid chain modification, is considered to be an important gut-brain signal for appetite control and energy balance. The ghrelin receptor, growth-hormone secretagogue receptor type 1a, is able to bind acylated ghrelin. The first recognised effect of ghrelin was the induction of growth hormone release from the somatotroph cells of the anterior pituitary. Moreover, by acting on vagal afferents or centrally, ghrelin can activate hypothalamic arcuate neurons that secrete the orexigenic peptides neuropeptide Y and agouti-related peptide, and inhibit the anorexigenic neurons secreting pro-opiomelanocortin and α-melanocyte-stimulating hormone. The orexigenic signalling pathway of ghrelin involves adenosine monophosphate-activated protein kinase. It has been proposed that ghrelin can also increase dopaminergic transmission from the ventral tegmental area to the nucleus accumbens, leading to augmentation of afferent reward signals. Present evidence suggests that ghrelin plays an important role in obesity, eating disorders, and cachexia, as well as in regulating appetite and energy balance in healthy individuals. In pathological states, ghrelin can be lower than normal as is seen in obese individuals, or can be higher than normal as has been reported for Prader-Willi syndrome, anorexia nervosa, bulimia nervosa, and certain types of cachexia. In the future, the application of compounds targeting the ghrelin pathway could involve the use of pharmacotherapies of ghrelin agonists, antagonists or inverse agonists, neutralisation of ghrelin by vaccines and spiegelmers, desacyl ghrelin analogues, as well as inhibitors of the GOAT enzyme which attaches the lipid modification to desacyl ghrelin to synthetise ghrelin.

The role of ghrelin in addiction: a review.

Ghrelin is a fast-acting hormone that is produced primarily by the stomach and by the brain although in smaller quantities. The regulation and the secretion of ghrelin are complex and not limited to aspects of feeding. Ghrelin exerts powerful effects on multiple processes, and it has been demonstrated that it mediates the rewarding properties of food as well as of drugs of abuse. The purpose of this review is to summarize the findings of preclinical and clinical studies related to ghrelin's possible role in addiction for each specific class of substances. Questions related to ghrelin's involvement in addiction are highlighted. Recurrent methodological issues that render the interpretation of the findings challenging are discussed. Also, the potential of targeting ghrelin as a pharmacologic treatment strategy for addiction is explored. Ghrelin signaling is implicated in the mediation of behavioral and biochemical effects of drugs of abuse that are cardinal for the development of addiction, especially for alcohol, nicotine, and stimulants. The available literature implicating ghrelin in opioid or cannabis use disorders is currently limited and inconclusive. There is intriguing, although not always consistent, evidence for the involvement of ghrelin signaling in aspects of addiction, especially in the cases of alcohol, nicotine, and stimulants. Further research, particularly in humans, is recommended to replicate and expand on the findings of the current literature. Improved and novel methodologies that take into account the volatile and complex nature of ghrelin are required to clarify the inconsistencies of the findings.

High Ghrelin Levels in Post-treatment Euthyroid Patients with Hashimoto’s Thyroiditis: a Case-control Preliminary Study

Hashimoto's thyroiditis is a chronic inflammatory condition often associated with changes in appetite and body composition. Ghrelin is an orexigenic peptide involved in the regulation of appetite and food intake. A possible role of ghrelin in mediating inflammation has been suggested. A few contrasting published data are available on the relationship between thyroid status and circulating ghrelin in patients affected by Hashimoto's thyroiditis. The aim of the present case-control study was to provide additional evidence on the relationship between thyroid status and plasma ghrelin levels in post-treatment euthyroid female patients with Hashimoto's thyroiditis, compared to healthy controls. 25 women [age 46.6±10.6 years; Body Mass Index 26.3±3.8 kg/m²] affected by overt hypothyroidism due to Hashimoto's thyroiditis were studied after thyroid hormones and body weight were already normalized for at least 2 months following L-thyroxine replacement. 25 healthy women (age 40.2±6.4 years; Body Mass Index 26.2±4.0 kg/m²) served as the control group. Blood levels of thyroid hormones, thyroid peroxidase antibodies, thyroglobulin antibodies and ghrelin were determined. Fat mass, fat-free mass and high-density lipoprotein cholesterol were also assessed. Circulating ghrelin levels were significantly higher in patients vs. control subjects (p<0.001). No differences were found in metabolic parameters (body mass index, fat mass, fat-free mass, high-density lipoprotein cholesterol) between groups. The present study provides additional evidence of hyperghrelinemia status in post-treatment euthyroid patients affected by Hashimoto's thyroiditis.

Ghrelin Receptor Ligands: Design and Synthesis of Pseudopeptides and Peptidomimetics

Mainly synthesized in the stomach, ghrelin is a peptide hormone which stimulates growth hormone secretion and appetite, thus promoting food intake and body-weight gain. Historically, researchers started to work on the discovery of ghrelin receptor ligands several years before the discovery of the ghrelin receptor and the hormone itself. Indeed peptides able to stimulate growth hormone secretion (growth hormone releasing peptides, GHRPs) were found while the mechanism of action and the target receptor were still unknown. Non peptidic agonists were then described (growth hormone secretagogues, GHSs) and the receptor (GHS-R1a) identified in 1996. Three years later, the natural ligand of this receptor (ghrelin) was isolated from stomach and its chemical synthesis allowed to show the physiological role of ghrelin in energy balance. In this review, we present some pseudopeptide and peptidomimetic approaches used by researchers for the design of ghrelin receptor ligands. We will start by the pioneering work of Bowers et al. on enkephalin analogues, which was the starting point for the development of an impressive number of compounds, by several of the major worldwide pharma companies. We will also describe the work achieved starting from a substance P derivative, which was one of the first peptides identified as an antagonist of the newly discovered ghrelin receptor. Then we will review the structure activity relationship study starting from the peptide ghrelin, which started with the discovery of this peptide in 1999. We will also focus on a more recent work based on macrocyclic peptidic analogues for the development of ghrelin receptor ligands.

Ghrelin receptors in human gastrointestinal tract during prenatal and early postnatal development

The aim of our study was to investigate the appearance, density and distribution of ghrelin cells and GHS-R1a and GHS-R1b in the human stomach and duodenum during prenatal and early postnatal development. We examined chromogranin-A and ghrelin cells in duodenum, and GHS-R1a and GHS-R1b expression in stomach and duodenum by immunohistochemistry in embryos, fetuses, and infants. Chromogranin-A and ghrelin cells were identified in the duodenum at weeks 10 and 11 of gestation. Ghrelin cells were detected individually or clustered within the base of duodenal crypts and villi during the first trimester, while they were presented separately within the basal and apical parts of crypts and villi during the second and third trimesters. Ghrelin cells were the most numerous during the first (∼11%) and third (∼10%) trimesters of gestation development. GHS-R1a and GHS-R1b were detected at 11 and 16 weeks of gestation, showed the highest level of expression in Brunner's gland and in lower parts of duodenal crypts and villi during the second trimester in antrum, and during the third trimester in corpus and duodenum. Our findings demonstrated for the first time abundant duodenal expression of ghrelin cells and ghrelin receptors during human prenatal development indicating a role of ghrelin in the regulation of growth and differentiation of human gastrointestinal tract.

Role of Ghrelin in Drug Abuse and Reward-Relevant Behaviors: A Burgeoning Field and Gaps in the Literature

Ghrelin is a gut-brain hormone that regulates energy balance through food consumption. While ghrelin is well known for its role in hypothalamic activation and homeostatic feeding, more recent evidence suggests that ghrelin also is involved in hedonic feeding through the dopaminergic reward pathway. This paper investigated how ghrelin administration (intraperitoneal, intracerebroventricular, or directly into dopaminergic reward-relevant brain regions) activates the dopaminergic reward pathway and associated reward-relevant behavioral responses in rodents. A total of 19 empirical publications that examined one or more of these variables were included in this review. Overall, ghrelin administration increases dopamine levels in the nucleus accumbens, as well as reward-relevant behaviors such as food (both standard chow and palatable foods) and alcohol consumption. Ghrelin administration also increases operant responding for sucrose, and conditioned place preference. Following a review of the small body of literature examining the effects of ghrelin administration on the dopamine reward pathway, we present a model of the relationship between ghrelin and dopaminergic reward activation. Specifically, ghrelin acts on ghrelin receptors (GHS-R1A) in the ventral tegmental area (VTA) and lateral dorsal tegmental nucleus (LDTg) to stimulate the mesolimbic dopamine reward pathway, which results in increased rewarding behaviors in rodents. Results from this review suggest that selective antagonism of the ghrelin system may serve as potential treatment for addictive drug use. This review highlights gaps in the literature, including a lack of examination of sex- or age-related differences in the effects of ghrelin on dopamine reward processes. In light of vulnerability to drug abuse among female and adolescent populations, future studies should target these individual difference factors.

Characterization of a murine model of septic cachexia

Muscular loss is a characteristic phenomenon induced by a massive inflammation as occurring in sepsis. Indeed, the early phase of sepsis is responsible for the expression of proinflammatory cytokines, namely TNFα and IL-6, known to be effectors of cachexia. Although cachexia is a morbidity factor in human, there is to date no animal model of septic cachexia. The goal of this study is to create and characterize a murine model of septic cachexia and evaluate endogenous ghrelin variations. Among the factors involved in both sepsis and muscular protection, current research highlights a potential role for ghrelin in muscle protection but there are conflicting data regarding its variations during experimental sepsis. In this study we evaluate its two circulating forms (AG, acylated ghrelin and UAG, unacylated ghrelin).

EFFECT OF GHRELIN ON TESTICULAR FUNCTIONS IN STREPTOZOTOCIN INDUCED TYPE 1 DIABETIC RATS

Physiology department-Faculty of medicine-Zagazig University Abstract Background: Oxidative stress is increased in Diabetes mellitus (DM). Ghrelin is a peptide hormone produced by different tissues and its circulating level is decreased in type 1 DM. Recently, it has been shown to have antioxidant properties. Objective: This study is designed to investigate the effects of diabetes mellitus on testicular functions and the role of ghrelin in the modulation of these effects in a rat model of type 1 diabetes mellitus induced by Streptozotocin. Materials and methods: 32 healthy adult albino male rats of 170-195 gm initial body weight were utilized. The Rats were randomly and equally divided into 4 groups, group (1a): Vehicle treated (control) group, group (1b): Ghrelin treated normal group, group (IIa): STZ-diabetic group and group (IIb): Ghrelin treated diabetic group. Rats were weighed and checked for the serum levels of glucose, insulin, FSH, LH& testosterone levels, epididymal sperm count and motility, testicular malondialdhyde (MDA) level and superoxide dismutase (SOD), catalase (CAT) & glutathione peroxidase (GPX) activities and testicular weight & histopathology. Results and discussion: STZ-induced diabetes significantly decreased body weight, testes weight, serum insulin, FSH, LH & testosterone levels, epididymal sperm count & motility and testicular SOD, CAT & GPX activities. However, they significantly increased serum glucose & testicular malondialdhyde levels parallel with deterioration of the testicular histoarchitecture. In addition, it was found that exogenous administration of ghrelin resulted in a significant recovery of the above mentioned parameters in the diabetic group, while in the normal group, it was only associated with potentiating of the testicular antioxidant system as well as a significant increase in the body and testes weights. Conclusion: Ghrelin has a potential protective role against diabetes-induced pituitary testicular dysfunction which may be due to its antioxidant properties and maintenance of glucose and insulin homeostasis.

Ghrelin receptor antagonism of morphine-induced accumbens dopamine release and behavioral stimulation in rats

Ghrelin, an orexigenic (appetite stimulating) peptide activates binding sites in the ventral tegmental area (a structure linked with the neural reward system) allowing it to participate in reward-seeking behavior. An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine, and nicotine abuse. However, the role of ghrelin, in opioid effects, has rarely been examined. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit markers of morphine-induced activation of the neural reward system, namely morphine-induced increase of dopamine in the nucleus accumbens and behavioral changes in rats. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens shell in rats following morphine (MO, 5, 10 mg/kg s.c.) administration with and without ghrelin antagonist pretreatment (JMV2959, 3, 6 mg/kg i.p., 20 min before MO). Induced behavioral changes were simultaneously monitored. JMV2959 significantly and dose dependently reduced MO-induced dopamine release in the nucleus accumbens shell and affected concentration of by-products associated with dopamine metabolism: 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). JMV2959 pretreatment also significantly reduced MO-induced behavioral stimulation, especially stereotyped behavior. Ghrelin secretagogue receptors (GHS-R1A) appear to be involved in the opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.

Role of Ghrelin in regulation of growth hormone secretion by Ghrelin-Pituitary-GH axis linkage

Background: Ghrelin is the endogenous ligand of the growth hormone (GH) secretagogue receptor and is the first hormone linking gastrointestinal-pituitary axis. Actions of ghrelin on GH secretion provide a strong force for envisioning that one of the major role of ghrelin could be the regulation of secretion of GH. Aims & Objective: To explore the intriguing dimensions on the possible physiological role of the Ghrelin /GHRP system. Materials and Methods: The search was performed in electronic databases (Medline, Embase, Cochrane, Google scholar) and by hand searching by 2 reviewers. Clinical trials (Randomised and non-randomised trials), review articles, systematic reviews, conference proceedings and meta-analysis were included in the study. Results: Ghrelin stimulates strong increase in circulating GH levels both in vitro and in vivo in a dose-dependent manner. Human or animal ghrelin was found to be significantly more potent than a synthetic GHS, hexarelin. The regulation of GH by Ghrelin is influenced by various other factors like autonomic nervous system, GHRH, IGF-1, anterior pituitary hormones, obesity, etc. Conclusion: Ghrelin is a specific endogenous ligand for the GHS receptor and suggests the existence of a GHS–GHS receptor signaling system in the regulation of GH secretion. Stomach-ghrelin - pituitary-GH axis links nutritional intake to regulation of GH secretion. However, the mechanism underlying the feedback actions of GH on the regulation of ghrelin remains unanswered. Under physiological conditions, ghrelin administered either centrally or peripherally, exerts a potent, time-dependent stimulation of pulsatile secretion of GH by ghrelin-pituitary-GH axis.

Role of Ghrelin, Leptin and Insulin Resistance in Development of Metabolic Syndrome in Obese Patients

Objective: Obesity and its complications including metabolic syndrome (MetS) have been increased in children and adolescents recently. Leptin is known to play an important role in the pathogenesis of obesity. The objective of this study was to evaluate the relationship between Leptin, Ghrelin and Insulin resistance in the development of metabolic syndrome in obese persons. Methods: this study was carried out on fifty obese persons. All patients have BMI ≥ 30 Kg/m2. Twenty of them have metabolic syndrome. Body Mass Index (BMI), Waist Circumference (WC), and blood pressure were measured. Fasting Plasma Glucose (FBG), two hours Post Prandial Blood Glucose (PPBG), Glycated hamoglobin A1C (HbA1c), triglyceride (TG), Total Cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), serum Leptin, Ghrelin and Insulin were done. HOMA-IR and HOMA- β were calculated. Results: SBP, DBP, FBS, PPBG, HbA1c, HOMA-IR and HOMA-β were significantly increased in obese and MetS groups compared to control group. There was a significant increase in insulin and Leptin, serum TG, TC and LDL-C with a significant decrease in HDL cholesterol and Ghrelin in obese and MetS groups. A significant negative correlation between plasma Ghrelin and BMI, WC, SBP, DBP, and FBS, PPBG, serum TG, TC, LDL-C, HbA1c, and HOMA-B was observed while leptin showed a significant positive correlation with them and a negative correlation with HOMA-IR. Plasma Ghrelin was positively correlated with HDL-C while Leptin was positively correlated with it in obese and MetS groups. There was a significant negative correlation between plasma Ghrelin, Insulin and leptin with significant positive correlation between plasma insulin and leptin in obese and MS groups. Conclusion: There are hormonal changes associated with clusters of metabolic abnormalities and elevation of blood pressure that may have a role in the development of MetS in obese persons and are major CHD risk factors. Insulin has stimulatory trophic effect on leptin secretion, but the effect of leptin on insulin is controversial as leptin may modulate insulin action and participates in the development of insulin resistance. As regard Ghrelin secretion, there are many suppressive factors: insulin, Leptin and glucose. Our study produces a preliminary result, thus further studies with large number of patients are required.

Somatotropic and cardio-protective effects of ghrelin in experimental models of heart failure: A systematic review

Background: Ghrelin was initially recognized as an endogenous ligand of growth hormone secretagogue receptor and was implicated in the regulation of food intake, and promoting weight gain. Ghrelin has been shown to improve cardiac function in patients suffering from heart failure (HF) though various mechanisms. The aim of the review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin on the cardiovascular system. Materials and Methods: All publications describing trials, systematic reviews, meta-analyses and review papers published within 1999-2014 of ghrelin in animal models of HF were sought through electronic and manual searches. Results: The literature searches identified 126 references and ten trials meeting the inclusion criteria were included in this review. All studies were carried out on male rats and experimental model of HF. Ghrelin has been shown to reduce mortality, increase appetite and body weight, and was found to improve the cardiac function parameters. Review found deficient information about adverse effects of ghrelin. Ghrelin exerts cardioprotective effects through modulation of sympathetic nervous system, inhibiting autophagy, antiinflammatory effects and protection against ischemia/reperfusion injury. Conclusion: Ghrelin seems to have a beneficial effect in rat models of HF and can offer an effective therapeutic target for improving outcome in HF.

Intraportal Infusion of Ghrelin Could Inhibit Glucose-Stimulated GLP-1 Secretion by Enteric Neural Net in Wistar Rat

As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.

Acute hormonal response to glucose, lipids and arginine infusion in overweight cats.

In cats, the incidence of obesity and diabetes is increasing, and little is known about specific aspects of the endocrine control of food intake in this species. Recent data suggest that ghrelin has an important role in the control of insulin secretion and vice versa, but this role has never been demonstrated in cats. Here we aimed to improve our understanding about the relationship between insulin, amylin and ghrelin secretion in response to a nutrient load in overweight cats. After a 16h fast, weekly, six overweight male cats underwent randomly one of the four testing sessions: saline, glucose, arginine and TAG. All solutions were isoenergetic and isovolumic, and were injected intravenously as a bolus. Glucose, insulin, acylated ghrelin (AG), amylin and prolactin were assayed in plasma before and 10, 20, 40, 60, 80 and 100min after the nutrient load. A linear mixed-effects model was used to assess the effect of bolus and time on the parameters. A parenteral bolus of glucose or arginine increased insulin and ghrelin concentrations in cats. Except for with the TAG bolus, no suppression of ghrelin was observed. The absence of AG suppression after the intravenous load of arginine and glucose may suggest: (1) that some nutrients do not promote satiation in overweight cats; or that (2) AG may be involved in non-homeostatic consumption mechanisms. However, the role of ghrelin in food reward remains to be assessed in cats.

Ghrelin promotes intestinal epithelial cell proliferation through PI3K/Akt pathway and EGFR trans-activation both converging to ERK 1/2 phosphorylation

Little is known about ghrelin's effects on intestinal epithelial cells even though it is known to be a mitogen for a variety of other cell types. Because ghrelin is released in close proximity to the proliferative compartment of the intestinal tract, we hypothesized that ghrelin may have potent pro-proliferative effect on intestinal epithelial cells as well. To test this hypothesis, we characterized the effects of ghrelin on FHs74Int and Caco-2 intestinal epithelial cell lines in vitro. We found that ghrelin has potent dose dependent proliferative effects in both cell lines through a yet to be characterized G protein coupled growth hormone secretagogue receptor (GHS-R) subtype. Consistent with above findings, cell cycle flowcytometric analyses demonstrated that ghrelin shifts cells from the G1 to S phase and thereby promotes cell cycle progression. Further characterization of subcellular events, suggested that ghrelin mediates its pro-proliferative effect through Adenylate cyclase (AC)-independent epidermal growth factor receptor (EGFR) trans-activation and PI3K-Akt phosphorylation. Both these pathways converge to stimulate MAPK, ERK 1/2 downstream. The role of ghrelin in states where intestinal mucosal injury and rapid mucosal repair occur warrants further investigation.

The role of ghrelin in drug and natural reward

Ghrelin is a protein that has been given special attention in both nutrition and addiction research during the last decade. Consequently, a vast amount of information has been accumulated concerning the role of ghrelin in natural and drug reward. We are now in the position to ask whether the ghrelin system could be targeted to treat maladaptive behaviours such as obesity and drug addiction. Indeed, ghrelin research has demonstrated that blocking the activity of ghrelin receptors may be effective in reducing the consumption of both food and drugs of abuse. This review will give a short overview of our current knowledge about the ghrelin system in the context of drug and natural rewards as well as the possibility of developing potential ghrelin-based treatments.

Reciprocal relationship between plasma ghrelin level and arterial stiffness in hypertensive subjects

Arterial stiffness, considered an independent predictor of cardiovascular morbidity and mortality, is closely associated with hypertension. Futhermore, the role of ghrelin in the development of hypertension has been widely recognized. The purpose of the present study was to explore the potential relationship between circulating ghrelin and arterial stiffness in hypertensive subjects. A total of 192 patients with primary hypertension and 107 normotensive (NT) control subjects were enrolled in the present cross-sectional study. Plasma ghrelin was determined by ELISA. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV) and the augmentation index (AIx). Both baPWV and AIx values were markedly higher in the hypertensive compared with NT group (P < 0.01). In contrast, plasma ghrelin concentrations were significantly lower in hypertensive patients compared with NT subjects (P < 0.01). Plasma ghrelin concentrations were negatively correlated with age (odds ratio (OR) -1.836; P < 0.001), smoking (OR -1.347; P = 0.042), baPWV (OR -1.762; P < 0.001) and AIx (OR -1.516; P = 0.005), but positively associated with fasting plasma glucose (OR 1.293; P = 0.047) and HbA1c (OR 1.413; P = 0.025). The inverse correlation between circulating ghrelin and the extent of arterial stiffness suggests that ghrelin is an independent determinant of arterial stiffness, even after adjustment for confounding cardiovascular risk factors, and it actively participates in the pathophysiology of arterial stiffness in hypertensive subjects.

Immunolocalisation of ghrelin and obestatin in human testis, seminal vesicles, prostate and spermatozoa

The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti-ghrelin and anti-obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.

Ghrelin Levels in Patients with Rickets

Rickets is a common metabolic bone disease in infants. The predominant cause of rickets is vitamin D deficiency. Vitamin D is required for bone formation. The role of ghrelin in bone metabolism is unclear, but it may have an indirect effect. There are also reports in the literature suggesting that ghrelin acts directly on osteoblasts as a positive regulator. To evaluate the relationship between ghrelin levels and the development of rickets. We evaluated the relationship between serum/ saliva ghrelin levels and rickets in a cohort of 10 patients aged 6-24 months with nutritional rickets and completely healthy 14 children. Plasma ghrelin levels were measured using a commercial radioimmunoassay kit. The saliva ghrelin measurements were performed using a Human-ghrelin- radioimmunoassay-sensitive kit. Ghrelin levels in blood and saliva were found significantly lower in the rickets group compared to the healthy subjects in this study. Findings of this study shows that there is a relationship between ghrelin and the development of rickets. Decreased ghrelin levels may have caused to poor infant appetite and impaired nutritional status. Furthermore the absence of ghrelin\'s calciotropic effects may have contributed to the development of rickets. Detailed studies with larger series are warranted to support these findings.

Role of Ghrelin and GH in Maintaining Glucose Homeostasis in Pregnant Mice During Calorie Restriction

Role of Ghrelin and GH in Maintaining Glucose Homeostasis in Pregnant Mice During Calorie Restriction