Biomedical subjects

Masayasu Kojima

Publications and source records attributed to Masayasu Kojima.

At least 55 records · Page 3Linked to original sources

PubMed2003

The role of circulating ghrelin in growth hormone (GH) secretion in freely moving male rats.

To examine the physiological significance of plasma ghrelin in generating pulsatile growth hormone (GH) secretion in rats, plasma GH and ghrelin levels were determined in freely moving male rats. Plasma GH was pulsatilely secreted as reported previously. Plasma ghrelin levels were measured by both N-RIA recognizing the active form of ghrelin and C-RIA determining total amount of ghrelin. Mean +/- SE plasma ghrelin levels determined by N-RIA and C-RIA were 21.6 +/- 8.5 and 315.5 +/- 67.5 pM, respectively, during peak periods when plasma GH levels were greater than 100 ng / ml. During trough periods when plasma GH levels were less than 10 ng / ml, they were 16.5 +/- 4.5 and 342.1 +/- 29.8 pM, respectively. There were no significant differences in plasma ghrelin levels between two periods. Next, effect of a GH secretagogue antagonist, [D-Lys-3]-GHRP-6, on plasma GH profiles was examined. There were no significant differences in both peak GH levels and area under the curves of GH (AUCs) between [D-Lys-3]-GHRP-6-treated and control rats. These findings suggest circulating ghrelin in peripheral blood does not play a role in generating pulsatile GH secretion in freely moving male rats.

Animals↗

PubMed2003

Effect of chronic treatments with ghrelin on milk secretion in lactating rats.

Ghrelin, a novel acylated peptide and endogenous ligand for growth hormone (GH) secretagogue receptor, was originally isolated from rat and human stomachs. In addition to its GH-releasing activity, ghrelin plays an important role in many physiological functions, including food intake, gastric acid secretion, neonatal development, and so on. In this study, the effect of daily treatment with ghrelin on milk production was investigated in lactating rats and the development of the pups was monitored. Daily subcutaneous injection of ghrelin into nursing dams for 8 days from parturition caused a significant increase in milk yield and litter weight gain. When litters nursed by ghrelin-treated and saline-treated dams were interchanged on day 4 of lactation, the growth curves were reversed. Daily injections of ghrelin also increased plasma GH levels. Northern blot analysis revealed that daily injection of ghrelin significantly increased mammary casein mRNA expression. In addition, RT-PCR analysis showed that a ghrelin receptor was present in the mammary glands of lactating rats. These results suggest that ghrelin may play an important role in milk production in lactating dams.

Animals↗

PubMed2003

Identification of tilapia ghrelin and its effects on growth hormone and prolactin release in the tilapia, Oreochromis mossambicus.

We have identified ghrelin and cDNA encoding precursor protein from the stomach of a euryhaline tilapia, Oreochromis mossambicus. The sequence of 20-amino acid tilapia ghrelin is GSSFLSPSQKPQNKVKSSRI. The third serine residue was modified by n-decanoic acid. The carboxyl-terminal end of the peptide possessed an amide structure. RT-PCR analysis revealed high levels of gene expression in the stomach and low levels in the brain, kidney and gill. Tilapia ghrelin stimulated growth hormone (GH) and prolactin (PRL) release from the organ-cultured tilapia pituitary at a dose of 10 nM. Thus, a novel regulatory mechanism of GH secretion by gastric ghrelin seems to be conserved in the tilapia. Stimulation of PRL release by homologous ghrelin has been reported in human, bullfrog and eel, and suggests the presence of growth hormone secretagogue receptor not only on somatotrophs but also on PRL cells of the tilapia pituitary.

Amino Acid Sequence↗

PubMed2003

Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans.

Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 microg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5 +/- 0.4 to 3.6 +/- 2.1 ng/ml (1 microg/kg ghrelin; P=0.99 compared with baseline), 27.1 +/- 12.0 ng/ml (5 microg/kg; P<0.01 compared with baseline) and 45.4 +/- 12.8 ng/ml (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 microg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5 +/- 0.6% to 65.1 +/- 0.9% (1 microg/kg ghrelin; P=0.97 compared with baseline), 69.6 +/- 1.3% (5 microg/kg; P<0.01 compared with baseline) and 71.5 +/- 0.9% (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.

Adrenocorticotropic Hormone↗

PubMed2003

The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis.

Recent research progress indicates a close link between ghrelin, a natural ligand of GH secretagogues receptor (GHS-R), and both the metabolic balance and body composition. To clarify the involvement of ghrelin and GHS-R in the process of adipogenesis, we measured the expression of GHS-R and peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma 2) mRNA in rat adipocytes using semiquantitative RT-PCR methods. The levels of GHS-R mRNA increased by up to 4-fold in adipose tissue from epididymal and parametrial regions as the rat aged from 4-20 wk and were significantly elevated during the differentiation of preadipocytes in vitro. Ghrelin (10(-8) M for 10 d) stimulated the activity of glycerol-3-phosphate dehydrogenase and the differentiation of rat preadipocytes in vitro. Ghrelin treatment also significantly increased the levels of PPAR-gamma 2 mRNA in primary cultured rat differentiated adipocytes. In addition, isoproterenol (10(-8) M, 40 min)-stimulated lipolysis was significantly reduced by simultaneous ghrelin treatment in a dose-dependent manner in vitro. In conclusion, the expression of GHS-R in rat adipocytes increases with the age and during adipogenesis. Ghrelin in vitro stimulates the differentiation of preadipocytes and antagonizes lipolysis. Ghrelin may therefore play an important role in the process of adipogenesis in rats.

Adipocytes↗

PubMed2003

Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts.

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-beta1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.

Age Factors↗

PubMed2003

Ghrelin is involved in the decidualization of human endometrial stromal cells.

Successful implantation involves a complex interaction between the endometrium and the embryo. It is well known that several neuropeptides are expressed in the endometrium and placenta during embryonal implantation, suggesting an important role as chemical mediators of the feto-maternal relationship. Ghrelin has recently been identified as the endogenous ligand for the GH secretagogue receptor. Ghrelin is a peptide hormone with many physiological functions, and its expression in the human placenta has been reported. To investigate the involvement of ghrelin in embryonal implantation, we assessed the spatio-temporal expression pattern of ghrelin and its receptor in the human endometrium and placenta through the normal menstrual cycle and in early pregnancy. We also examined the effect of ghrelin on the decidualization of endometrial stromal cells (ESC). Weak expression of ghrelin mRNA was detected in the nonpregnant endometrium, and it was dramatically increased in the decidualized endometrium. A GH secretagogue receptor mRNA was detected in the endometrium throughout the normal menstrual cycle and in early pregnancy, but not in the first trimester placenta. Immunohistochemical analysis using an antighrelin antibody revealed strong signals in decidual cells and extravillous trophoblast cells. Coculture with first trimester placenta up-regulated ghrelin mRNA expression by primary cultured ESC, although sex steroids and 8-bromo-cAMP had no effect. In addition, ghrelin enhanced the decidualization of ESC induced by 8-bromo-cAMP (8-Br-cAMP) in vitro. Thus, ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2003

Effects of ghrelin on growth hormone secretion from cultured adenohypophysial cells in cattle.

To clarify the direct effects of ghrelin on growth hormone (GH) release from anterior pituitary (AP) cells in cattle, GH-releasing effects of human ghrelin (hGhrelin) and rat ghrelin (rGhrelin) on bovine AP cells were compared with those of GH-releasing hormone (GHRH) in vitro. The AP cells were obtained from Holstein steers and were incubated for 2 h with the peptides after incubating in DMEM for 3 days. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses from 10(-10) to 10(-7) M and from 10(-9) to 10(-7) M, respectively (P<0.05). The rates of increase in GH at 10(-10), 10(-9), 10(-8) and 10(-7) M hGhrelin were 26, 26, 59 and 100% compared with controls, respectively, and those of increase in GH at 10(-9), 10(-8) and 10(-7) M rGhrelin were 58, 74 and 106%, respectively. GHRH significantly increased GH concentrations in cultured media at a dose as low as 10(-13) M compared with the control (P<0.05). When hGhrelin (10(-8) M) and GHRH (10(-8) M) were added together, the release of GH induced by both peptides was significantly greater than that by hGhrelin alone (P<0.05), and tended to be greater than that by GHRH alone. Somatostatin (SS, 10(-7) M) significantly blunted GH release induced by hGhrelin (10(-8) M) and GHRH (10(-8) M) (P<0.05). In the presence of SS, the percent increase in GH released with hGhrelin plus GHRH was 42% and 14% greater than that by either hGhrelin or GHRH alone, respectively (P<0.05). These results show that ghrelin directly stimulates the release of GH from anterior pituitary cells, and that SS modifies ghrelin-stimulated GH release in cattle.

Animals↗

PubMed2003

Increased plasma ghrelin level in lung cancer cachexia.

PURPOSE: Ghrelin, a novel growth hormone-releasing peptide,has been shown to cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in cachexia associated with lung cancer. EXPERIMENTAL DESIGN: Plasma ghrelin level was measured in 43 patients with lung cancer and 21 control subjects. Patients with lung cancer were divided into two groups: patients with cachexia (n = 21) and those without cachexia (n = 22). RESULTS: Plasma ghrelin level did not significantly differ between all patients with lung cancer and controls (157 +/- 10 versus 132 +/- 8 fmol/ml, P = 0.1). However, plasma ghrelin level was significantly higher in patients with cachexia than in those without cachexia (180 +/- 17 versus 135 +/- 10 fmol/ml, P = 0.011). Furthermore, plasma ghrelin level increased significantly in patients with decreased food intake after chemotherapy (from 136 +/- 11 fmol/ml to 170 +/- 16 fmol/ml on day 8, 179 +/- 20 fmol/ml on day 21 after start of chemotherapy), although plasma ghrelin level did not significantly change in those without decreased food intake. CONCLUSIONS: Baseline plasma ghrelin level was elevated in cachectic patients with lung cancer, and follow-up plasma ghrelin level increased in patients with anorexia after chemotherapy. Considering the positive energy effects induced by ghrelin, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer.

Aged↗

PubMed2002

A transient surge of ghrelin secretion before feeding is modified by different feeding regimens in sheep.

Ghrelin is a recently identified orexigenic hormone secreted by the stomach and has been implicated in meal-time hunger. Several experiments demonstrate a transient surge in ghrelin secretion shortly before a scheduled meal, suggesting from the involvement of cephalic mechanisms. If ghrelin secretion is stimulated by hunger in sheep, plasma levels of ghrelin should be modified by different feeding regimens that affect hunger drive. To test this hypothesis, we investigated changes in plasma ghrelin concentrations in fed Suffolk rams ad libitum and in rams either twice or four times daily. Plasma ghrelin levels increased (P<0.05) abruptly just before every feeding period in sheep fed twice and four times daily and then fell shortly after feeding. Peak levels of the pre-prandial ghrelin surge were higher (P<0.01) in animals fed twice daily than in animals fed four times daily, leading to greater (P<0.05) areas under response curves over 12h. In contrast, the plasma ghrelin levels remained relatively low and constant in sheep fed ad libitum, with no evidence of surges in plasma ghrelin levels. These results confirm that the transient surge in plasma ghrelin levels occurs just before feeding and demonstrate that this can be modified by the feeding regimen in sheep.

Animals↗

PubMed2002

Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing.

Ghrelin, a novel 28-amino acid peptide with an n-octanoyl modification at Ser(3), was isolated from rat stomach and found to be an endogenous ligand for the growth-hormone secretagogue receptor (GHS-R). This octanoyl modification is essential for ghrelin-induced GH release. We report here the purification and identification of human ghrelin from the stomach, as well as structural analysis of the human ghrelin gene and quantitation of changes in plasma ghrelin concentration before and after gastrectomy. Human ghrelin was purified from the stomach by gel filtration and high performance liquid chromatography, using a ghrelin-specific radioimmunoassay and an intracellular calcium influx assay on a stable cell line expressing GHS-R to test the fractions. In the course of purification, we isolated human ghrelin of the expected size, as well as several other ghrelin-derived molecules. Classified into four groups by the type of acylation observed at Ser(3); these peptides were found to be non-acylated, octanoylated (C8:0), decanoylated (C10:0), and possibly decenoylated (C10:1). All peptides found were either 27 or 28 amino acids in length, the former lacking the C-terminal Arg(28), and are derived from the same ghrelin precursor through two alternative pathways. The major active form of human ghrelin is a 28-amino acid peptide octanoylated at Ser(3), as was found for rat ghrelin. Synthetic octanoylated and decanoylated ghrelins produce intracellular calcium increases in GHS-R-expressing cells and stimulate GH release in rats to a similar degree. Both ghrelin and the ghrelin-derived molecules were found to be present in plasma as well as stomach tissue. Plasma levels of immunoreactive ghrelin after total gastrectomy in three patients were reduced to approximately half of their pre-gastrectomy values, after which they gradually increased. This suggests that the stomach is the major source of circulating ghrelin and that other tissues compensate for the loss of ghrelin production after gastrectomy.

Aged↗

PubMed2002

Immunohistochemical localization and biochemical characterization of ghrelin in the brain and stomach of the frog Rana esculenta.

Ghrelin is a 28-amino acid n-octanoylated peptide recently isolated from the rat stomach as an endogenous ligand of the growth hormone secretagogue receptor. So far, the occurrence of ghrelin has not been investigated in submammalian vertebrates. In the present work, we have studied the anatomic distribution and biochemical characterization of ghrelin-like immunoreactivity in the brain and stomach of the frog Rana esculenta by using two distinct antisera directed against rat ghrelin. In the brain, sparse ghrelin-positive cells were detected in three nuclei of the diencephalon, namely the suprachiasmatic nucleus and the posterior tuberculum in the hypothalamus, and the posterodorsal aspect of the lateral nucleus in the thalamus. A few ghrelin-immunoreactive neurons were also found in the mesencephalon, i.e., in the pretoral gray and the anterodorsal tegmental nucleus. Ghrelin-containing fibers were widely distributed in the frog brain. In particular, diffuse networks of immunoreactive processes were observed in various regions of the telencephalon, including the medial pallium, the striatum, the nucleus of the diagonal band of Broca, the nucleus accumbens, and the amygdala. In the diencephalon, the magnocellular nucleus, the suprachiasmatic nucleus, the posterior tuberculum, and the ventrolateral and lateral thalamic nuclei were moderately to densely innervated with ghrelin-containing fibers. A moderate density of positive fibers was also found in different areas of the mesencephalon such as the nucleus of the medial longitudinal fasciculus, the pretoral gray, and the tegmentum. In the stomach, a few brightly immunofluorescent cells were detected in the mucosa. The distribution pattern and morphologic characteristics of ghrelin-containing cells in the stomach suggest that they correspond to endocrine cells. Reversed-phase high performance liquid chromatography analysis of frog brain and stomach extracts, combined with RIA detection, revealed that ghrelin-immunoreactive material eluted as a single peak with a retention time slightly shorter than that of synthetic rat ghrelin. The present data provide the first evidence that a ghrelin-related peptide is present in submammalian vertebrates. The occurrence of ghrelin-containing cells in the hypothalamus and the stomach mucosa suggests that, in amphibians, ghrelin may exert both neuroendocrine and endocrine activities.

Animals↗

PubMed2002

Alteration of plasma ghrelin levels associated with the blood pressure in pregnancy.

Ghrelin, an endogenous ligand for the growth hormone secretagogues, was originally isolated from rat stomach. It stimulates the release of growth hormone from primary pituitary cell cultures. We investigated the plasma concentration of ghrelin peptide in 16 nonpregnant women, 18 normal pregnant women, 20 patients with pregnancy-induced hypertension, and 10 postpartum women. The plasma concentration of ghrelin in nonpregnant women was 239.5+/-16.9 fmol/mL. The plasma concentration of ghrelin in normal pregnant women at the third trimester was 127.1+/-5.6 fmol/mL. There was negative correlation between plasma ghrelin concentration and systemic blood pressure in normal pregnant women (systolic: r=-0.564, P<0.05; diastolic: r=-0.610, P<0.01). Pregnant women with pregnancy-induced hypertension (177.9+/-14.6 fmol/mL, P<0.05) also had significantly higher levels of ghrelin compared with those of normal pregnant women. In addition, there was a significant correlation between plasma ghrelin levels and systemic blood pressure (systolic: r=-0.482, P<0.05; diastolic: r=-0.466, P<0.05). These results suggest for the first time that ghrelin might have some role in cardiovascular control during normal pregnancy and in pathophysiological conditions in pregnancy, such as pregnancy-induced hypertension.

Adult↗

PubMed2002

Ghrelin, an orexigenic signaling molecule from the gastrointestinal tract.

Recent identification of novel appetite-regulating hormones has revealed the complex interactions between these humoral factors in the regulation of feeding behavior in mammals. One such hormone is ghrelin, which is a natural ligand of the orphan growth hormone secretagogue receptor. Ghrelin was first purified from rat stomach and is able to stimulate growth hormone release from pituitary cells. Ghrelin is a peptide of 28 amino acids, in which Ser3 is modified by an n-octanoic acid. This modification is essential for the activity of ghrelin. The peptide regulates food intake by acting on the hypothalamic arcuate nucleus, which is a region known to control food intake. Thus, gastric ghrelin is an endogenous regulator of feeding behavior that is found in both peripheral tissues and the central nervous system.

Amino Acid Sequence↗

PubMed2002

Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose.

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which may also cause a positive energy balance by stimulating food intake and reducing fat utilization. However, whether glucose influences the release of ghrelin remains unknown. Accordingly, we examined circulating levels of ghrelin and GH in response to the intravenous or oral administration of 50 g of glucose in eight healthy humans. After the administration of intravenous glucose (50 g), the plasma ghrelin level decreased significantly from 127+/-9 to 98+/-9 fmol/ml (P<0.01), associated with an increase in plasma glucose from 85+/-3 to 357+/-19 mg/dl (P<0.01). Ingestion of 50 g of glucose decreased the plasma ghrelin level significantly from 134+/-12 to 97+/-15 fmol/ml (P<0.01), associated with an increase in plasma glucose from 93+/-3 to 166+/-10 mg/dl (P<0.01). The decrease in the plasma ghrelin level lasted for more than 30 min after recovery of the plasma glucose level. In conclusion, ghrelin secretion may be suppressed, at least in part, by an increased plasma glucose level in healthy humans.

Administration, Oral↗

PubMed2002

Weight loss increases circulating levels of ghrelin in human obesity.

OBJECTIVE: Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to have adipogenic actions and induce weight gain in addition to its GH-releasing properties. Interestingly, recent data indicate that ghrelin is downregulated in human obesity, which is also known to be accompanied by reduced GH levels. PATIENTS AND METHODS: To investigate the influence of weight loss on circulating levels of ghrelin we recruited eight obese women among patients attending a 6-month weight-loss course organized by The Danish Heart Association. We measured body composition including computerized tomography as well as fasting plasma ghrelin concentrations before and after weight loss. RESULTS: Plasma ghrelin concentrations increased by 12% following weight loss (P < 0.01), and the increase in ghrelin levels was positively correlated with the extent of weight loss (r = 0.68, P < 0.05). Exposure to exogenous GH intravenously did not influence fasting ghrelin levels either before or after weight loss. Our data further suggest the existence of hyperghrelinaemia in a single subject with long-standing obesity but no signs of GH excess. CONCLUSIONS: This study provides evidence of a reversible suppression of ghrelin associated with obesity. The feasibility of measuring ghrelin in the circulation provides a new tool for the investigation of the complex hormonal regulation of appetite and energy balance.

Analysis of Variance↗

PubMed2002

Ghrelin immunoreactivity in human plasma is suppressed by somatostatin.

OBJECTIVE: Ghrelin was recently identified as a specific endogenous ligand for the growth hormone secretagogue receptor (GHS-R). This new hormone was isolated from rat and human stomach and was reported to circulate in human plasma, but the regulation and physiological significance of ghrelin in humans have not been clarified. The present study was undertaken to test the following hypotheses: (1) prolonged fasting, which is known to stimulate GH secretion, is associated with changes in ghrelin immunoreactivity; (2) somatostatin in the systemic circulation regulates ghrelin secretion; and (3) GH affects ghrelin levels. DESIGN AND PATIENTS: The study population included normal subjects investigated on three occasions (fasting alone, fasting and somatostatin infusion +/- GH); GH-deficient adults investigated after 12 and 36 h of fasting +/- GH, as well as patients with active acromegaly before and after somatostatin analogue treatment. RESULTS: Somatostatin infusion lowered ghrelin levels 70-80% (P < 0.0001), whereas continued fasting +/- GH did not significantly affect ghrelin levels. In active acromegaly, suppression of plasma ghrelin levels was recorded after a single subcutaneous octreotide injection as well as during prolonged administration of slow-release octreotide. CONCLUSIONS: (1) Amplification of GH release during prolonged fasting is not caused by an increase in ghrelin immunoreactivity, (2) systemic somatostatin suppresses plasma ghrelin levels independently of GH status, and (3) the feasibility of measuring ghrelin in the circulation provides an opportunity for studying the interaction between hormones and nutrition.

Acromegaly↗

PubMed2002

Ghrelin: a novel peptide for growth hormone release and feeding regulation.

PURPOSE OF REVIEW: A novel peptide hormone, ghrelin, has been identified from the stomach and recognized as an important regulator of growth hormone release and energy homeostasis. It is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. Thus, we summarize the recent findings on the mechanism of these effects induced by ghrelin. RECENT FINDINGS: The coadministration of ghrelin and growth hormone releasing hormone was found to have a synergistical effect on pituitary growth hormone secretion. The infusion of growth hormone releasing hormone in rats resulted in a significant increase in pituitary gene expression of ghrelin and its receptor system, suggesting that this system in the pituitary gland could modulate the regulation of growth hormone secretion by growth hormone releasing hormone. Ghrelin promoted the production of orexigenic neuropeptides (neuropeptide Y and agouti-related protein) in the hypothalamic arcuate nuclei and activated the neurons which produce these orexigenic neuropeptides, resulting in an increase in feeding and body weight. Gastric acid release and pancreatic protein secretions were also regulated by ghrelin through vagal and intrapancreatic neuronal activation, respectively. It is possible that ghrelin may participate in the regulation of cell proliferation, glucose homeostasis, and the immune system. SUMMARY: Ghrelin, secreted from the stomach, modulates growth hormone release and feeding promotion. Further elucidation of the mechanisms of ghrelin effects will help to improve the diagnosis and treatment of eating disorders and disturbed conditions of nutritional homeostasis.

Animals↗