生长激素促分泌素受体对小鼠结肠动力的影响和机制

目的:探讨生长激素促分泌素受体及其激动剂GHRP-6对小鼠结肠动力的影响及机制。方法:小鼠随机分组后,分别注射生理盐水、GHRP-6(20、50、100、200μg/kg),用炭末推进实验的方法研究GHRP-6对小鼠结肠推进的影响。小鼠近端结肠环形平滑肌条安置在恒温灌流肌槽中,并用SMUP-E生物信号处理系统记录肌条的自发收缩活动,观察不同浓度的GHRP-6(0.01、0.1、1和10μmol/L)对肌条自发收缩幅度的影响,以及神经阻断剂TTX和GHS-R阻断剂D-lys3-GHRP-6孵育肌条情况下,GHRP-6对肌条自发收缩幅度的影响。结果:GHRP-6注射剂量在50、100、200μg/kg时均能显著提高小鼠的结肠推进(P0.05)。GHRP-6浓度在0.1、1和10μmol/L时均能显著增加小鼠近端结肠环形平滑肌条的自发收缩幅度(P0.05),在TTX和D-lys3-GHRP-6孵育肌条下,Ghrelin不能增加小鼠结肠环形平滑肌条的自发收缩幅度。结论:GHRP-6可以显著增加小鼠的结肠推进,其机制可能是通过肠肌间神经丛的的GHS-R受体而起作用。     

生长激素释放肽ghrelin对小鼠结肠动力的影响

目的 探讨生长激素促分泌素受体(growth hormone secretagogue receptor,GHSR)内源性激动剂生长激素释放肽ghrelin对小鼠结肠动力的影响.方法 小鼠按随机数字法分组后,分别注射生理盐水和不同剂量ghrelin(20,50,100,200 ng/g),用炭末推进实验的方法观察ghrelin对小鼠结肠推进的影响,研究阿托品、NG-硝基精氨酸甲酯和D-Lys3-GHRP-6(GHSR阻断剂)对ghrelin(100 ng/g)引起的小鼠结肠推进改变的影响.将小鼠近端结肠环形平滑肌条安置在恒温灌流肌槽中并用SMUP-E生物信号处理系统记录肌条的自发收缩活动,观察不同浓度的ghrelin(0.01、0.1、1和10 μmol/L)对肌条自发收缩幅度的影响.结果 ghrelin能显著提高小鼠的结肠推进速度,有明显的量效关系.阿托品、NG-硝基精氨酸甲酯、D-lys3-GHRP-6均能显著抑制ghrelin促进结肠推进的作用(t=10.230,12.560,11.590,P＜0.05).ghrelin能显著增加小鼠近端结肠环形平滑肌的自发收缩幅度,河豚毒素预处理肌条后ghrelin不能显著增加肌条的自发收缩幅度.结论 ghrelin可以显著增加小鼠结肠的推进,可能是通过结肠肌间神经丛的硝基能神经和胆碱能神经上的GHSR而起作用.     

生长激素促分泌素参与大鼠小肠平滑肌运动的双相调节

目的探讨生长激素促分泌素（ghrelin）对大鼠小肠平滑肌舒缩活动的影响及其机制。方法制备迷走神经切断大鼠模型,腹腔注射不同浓度ghrelin（0、20、40和80μg／kg）,每种浓度6只大鼠,观察其对小肠转运的影响。体外实验观察在50nmol／L卡巴胆碱（Cch）存在时,不同浓度的ghrelin（0．01、0．1、0．5、1．0μmol／L）对肌条舒缩活动的影响,免疫荧光方法检测ghrelin受体（GHS．R1a）在小肠肌层中不同类型细胞的分布。结果0、20、40和80Ixg／kg4种浓度的ghrelin能够剂量依赖性地增加小肠转运率,分别为（25．4±1．0）％、（33．7±1．9）％、（39．3±2．4）％和（44．7±2．1）％,组间比较差异有统计学意义（P〈0．05）。体外应用0．01、0．1、0．5和1．0μmol／L4种浓度的ghrelin能剂量依赖增强Cch引起的肌条收缩[（67．0±2．4）％、（149．5±3．3）％、（187．1±4．7）％、（213．5±3．4）％]和舒张[（35．3±1．1）％、（62．9±3．8）％、（79．6±2．7）％、（94．6±2．2）％]效应,组问比较差异均有统计学意义（均P〈0．05）。免疫荧光检测显示,ghrelin受体主要分布在肠内肌层中的神经细胞膜上,平滑肌细胞膜上无分布。结论ghrelin可通过直接作用于小肠肌层神经丛中的神经细胞而增强胆碱能神经递质引起的小肠平滑肌的舒缩活动。     

Ghrelin对糖尿病小鼠结肠动力的影响及机制

目的：探讨生长激素促分泌素受体（GHS-R）内源性激动剂Ghrelin对糖尿病小鼠结肠动力的影响,进一步探讨其作用机制。方法：建立糖尿病小鼠模型,用炭末推进实验测定正常小鼠和糖尿病小鼠的结肠推进率,分析Ghrelin、阿托品、L-NAME和D-lys3-GHRP-6对糖尿病小鼠结肠转运的影响,并观察Ghrelin和河豚毒素（TTX）在体外对糖尿病小鼠近端环形平滑肌条自发收缩活动的影响。结果：糖尿病小鼠的结肠推进率为（34.70±1.42）%,正常小鼠的结肠推进率为（39.70±1.78）%,二者差异有统计学意义（P〈0.05）。Ghrelin注射剂量为50、100、200μg/kg时糖尿病小鼠结肠推进率均显著提高,分别为（40.10±1.23）%、45.30±2.32）%、56.40±2.81）%,有明显的量效关系（P〈0.05）。而阿托品、（（L-NAME和D-lys3-GHRP-6均能抑制Ghrelin增加糖尿病小鼠结肠推进率的效应。在体外,Ghrelin浓度在0.1、1和10μmol/L时均可显著增加肌条的自发收缩幅度,分别增加至不加药情况下的（1.12±0.04）、1.23±0.03）和（1.35±0.04）倍,有明显的量效关系（P〈0.05）,能阻断该效应。结论：Ghrelin（TTX能提高糖尿病小鼠的结肠动力,其作用机制可能是通过肌间神经丛系统的硝基能神经和胆碱能神经上的受体而起作用。     

Ghrelin受体表达对大鼠胃肠手术后小肠动力不足的影响

目的探讨ghrelin受体变化对大鼠术后小肠动力不足的影响。方法采用体外肌条实验观察在卡巴胆碱（10nmol／L）存在和缺乏时,不同浓度的ghrelin（0、0．01、0．1、0．5、1．0μmol／L）对肌条收缩力的影响。采用免疫组织化学方法和Westemblot技术检测行端侧肠吻合的实验组大鼠和行假手术的对照组大鼠小肠肌层ghrelin受体（GHS—R1a）的表达情况。结果在体外,卡巴胆碱存在时,ghrelin能够增强小肠平滑肌肌条的收缩,不同浓度的ghrelin（0．1、0．5、1．0la,mol／L）引起的收缩力差异具有统计学意义[（223±18）％、（245±22）％、（264±25）％,P〈0．01]。免疫组化染色显示．GHS—R1a主要分布于小肠肌层．实验组大鼠小肠环形肌和纵行肌中GHS—R1a表达均弱于对照组。Westernblot结果显示,实验组小肠ghrelin受体表达量（0．51±0．02）明显低于对照组（0．71±0．01,P〈0．01）。结论术后小肠肌层ghrelin受体表达下调所导致的ghrelin效应减弱可能参与术后小肠动力不足的发生。     

哌替啶和氯胺酮对离体大鼠视上核神经元自发放电频率的影响

目的 观察静脉麻醉药氯胺酮和麻醉性镇痛药哌替啶对离体大鼠视上核（SON）神经元自发放电频率的影响。方法 将新生SD大鼠迅速断头取脑，置于通入95％O2和5％CO2混合气体的4℃人工脑脊液（ACSF）中，以振动切片机制成300—400μm含SON神经元的脑薄片，将脑薄片随机分为6组：哌替啶50μmol／L组、100μmol／L组、150μmol／L组和氯胺酮50μmol／L组、100μmol／L组、150μmol／L组，每组30张脑片，应用全细胞膜片钳记录技术观察给药前、给药后5min和正常ACSF冲洗后5min各组SON神经元自发放电频率。结果 与给药前即刻比较，3组灌流5min后、哌替啶150wnol／L组冲洗5min后SON神经元自发放电频率下降（P〈0．05或0．01）；与哌替啶50μmol／L组比较，100μmol／L组和150μmol／L组灌流5min后、冲洗5min后SON神经元自发放电频率下降（P〈0．05或0．01）。与给药前即刻比较，氯胺酮100μmol／L组和150μmol／L组灌流5min后、150μmol／L组冲洗5min后SON神经元自发放电频率下降（P〈0．05或0．01）；与氯胺酮50μmol／L组比较，氯胺酮100μmol／L组和150μmol／L组灌流5min后、150μmol／L组冲洗5min后SON神经元自发放电频率下降（P〈0．05或0．01）。结论 哌替啶和氯胺酮对大鼠SON神经元自发放电频率可产生明显可逆性的抑制作用。     

抗胃食管反流手术对大鼠胃排空功能影响的实验研究

目的 观察不同抗胃食管反流手术对大鼠胃排空功能的影响。方法 将大鼠随机分为5组，A组为贲门肌层切开组，B组为贲门肌层切开后行Nissen手术，C组为贲门肌层切开后行Nissen手术并加行幽门肌层切开，D组为贲门肌层切开加贲门斜行套叠术，E组为对照组。于第4周行放射性核素胃排空功能检查，观察手术对大鼠胃排空功能的影响。结果 （1）半胃排空时间C组较B、D组快（P＜0．05），B、C、D组较E组快（P＜0．05），A组与E组无差别（P＞0．05）。（2）2h胃内放考元素潴留率测定表明，A组与E组无差别（P＞0．05），B、C、D组较E组少（P＜0．05），B、C、D组间无差别（P＞0．05）。结论 （1）抗反流手术（Nissen手术、贲门斜行套叠术）可以使半胃排空时间增快，2h胃内放射性元素潴留率减少。（2）Nissen手术加做幽门肌层切开可使半胃排空时间增快，但2h胃内放射性元素潴留率较单纯Nissen术无变化，综合考虑，行抗反流手术不必同时加行幽门肌层切开术。     

生长抑素抑制人结肠癌细胞增殖的实验研究

目的：研究外源性生长激素（GH）和生长抑素（SS）对人结肠癌细胞株HT-29的影响，并探讨其作用机制。方法：人结肠癌细胞株HT-29分成正常对照组、生长抑素组（SS组）、生长激素组（GH组）和生长抑素＋生长激素组（GH＋SS组）。MTT法测定细胞抑制率，流式细胞仪测定细胞周期分布、增殖指数、凋亡率，RT—PCR方法测定bcl．2及baxmRNA水平。结果：生长抑素能够明显抑制人结肠癌细胞株HT-29增殖（P〈0．01）、降低S期和G2／M期细胞比例（P〈0．05）、降低增殖指数（PI）（P〈0．05）、促进细胞凋亡（P〈0．01）、降低bcl-2mRNA表达（P〈0．05）、提高baxmRNA表达（P〈0．01），生长激素则无明显作用。GH＋SS组表现与SS组相似。结论：生长抑素可能通过抑制GdG．期细胞进入S期和G2／M期以及促进细胞凋亡两种途径抑制体外培养的人结肠癌细胞株HT-29增殖。生长抑素可能是通过改变bax基因和bcl-2基因的表达影响肿瘤细胞的凋亡。生长激素对体外培养的人结肠癌细胞株HT-29无显著影响。     

半胱胺对大鼠生长及安全性的影响

为了研究半胱胺对动物生长和安全性的长期影响，分别对大鼠以0，20，35，50mg／kg注射半胱胺，以及以0，15，30，60mg／kg饲喂添加半胱胺．试验发现：每天注射20mg／kg半胱胺（以体重计）1周能明显提高大鼠的增重（P〈0．05），而其他组与对照组差异不显著（P〉0．05），而1周后的增重与对照组差异不显著；注射半胱胺11天，大鼠血液生长激素水平没有提高．在饲料中添加30mg／kg半胱胺，第1周显著提高大鼠增重（P〈0．05），而其他组与对照组差异不显著（P〉0．05）；1周后添加半胱胺的各组大鼠增重均没有提高；各组大鼠的肝脏、脾脏和肾脏指数差异不显著；血液中谷丙转氨酶有所降低，而谷草转氨酶和碱性磷酸酶没有影响．实验结果表明：腹腔注射和饲料添加半胱胺对大鼠的促生长作用均是短期的，即在1周之内有促进生长作用，长期添加或注射半胱胺不能显著提高大鼠增重．在本试验的时间和剂量范围内，半胱胺对大鼠的器官形态和功能没有表现出异常影响．     

生长激素和生长抑素对人结肠癌裸鼠移植瘤模型的影响

目的观察外源性生长激素（GH）和生长抑素（SS）对人结肠癌细胞株HT-29裸鼠移植瘤模型肿瘤生长和裸鼠血清蛋白水平的影响。方法接种结肠癌细胞株HT-29建立裸鼠移植瘤模型。比较移植肿瘤体积、细胞周期分布、增殖指数（PI）、凋亡率、bcl-2和bax mRNA水平．以及裸鼠血清蛋白水平。结果生长抑素能够明显抑制移植瘤的生长（P〈0．05）、降低移植瘤PI（P〈0．05）、促进移植瘤细胞凋亡（P〈0．01）、降低移植瘤bcl-2mRNA表达（P〈0．05）、提高移植瘤baxmRNA表达（P〈0．05），生长激素则表现出相反的作用。生长激素能够改善移植瘤导致的低蛋白血症（P〈0．05）。结论外源性生长抑素能够显著抑制人结肠癌裸鼠移植瘤生长，外源性生长激素单独或联合生长抑素应用能够改善荷人结肠癌移植瘤裸鼠低蛋白血症，但具有潜在的促进肿瘤生长的作用。     

Ghrelin directly regulates bone formation.

To clarify the role of ghrelin in bone metabolism, we examined the effect of ghrelin in vitro and in vivo. Ghrelin and its receptor, GHS-R1a, were identified in osteoblasts, and ghrelin promoted both proliferation and differentiation. Furthermore, ghrelin increased BMD in rats. Our results show that ghrelin directly affects bone formation. INTRODUCTION: Ghrelin is a gut peptide involved in growth hormone (GH) secretion and energy homeostasis. Recently, it has been reported that the adipocyte-derived hormone leptin, which also regulates energy homeostasis and opposes ghrelin's actions in energy homeostasis, plays a significant role in bone metabolism. This evidence implies that ghrelin may modulate bone metabolism; however, it has not been clarified. To study the role of ghrelin in skeletal integrity, we examined its effects on bone metabolism both in vitro and in vivo. MATERIALS AND METHODS: We measured the expression of ghrelin and growth hormone secretagogue receptor 1a (GHS-R1a) in rat osteoblasts using RT-PCR and immunohistochemistry (IHC). The effect of ghrelin on primary osteoblast-like cell proliferation was examined by recording changes in cell number and the level of DNA synthesis. Osteoblast differentiation markers (Runx2, collagen alpha1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined calcium accumulation and ALP activity in osteoblast-like cells induced by ghrelin. Finally, to address the in vivo effects of ghrelin on bone metabolism, we examined the BMD of Sprague-Dawley (SD) rats and genetically GH-deficient, spontaneous dwarf rats (SDR). RESULTS: Ghrelin and GHS-R1a were identified in osteoblast-like cells. Ghrelin significantly increased osteoblast-like cell numbers and DNA synthesis in a dose-dependent manner. The proliferative effects of ghrelin were suppressed by [D-Lys(3)]-GHRP-6, an antagonist of GHS-R1a, in a dose-dependent manner. Furthermore, ghrelin increased the expression of osteoblast differentiation markers, ALP activity, and calcium accumulation in the matrix. Finally, ghrelin definitely increased BMD of both SD rats and SDRs. CONCLUSIONS: These observations show that ghrelin directly stimulates bone formation.     

Ghrelin attenuates the inhibitory effects of glucagon-like peptide-1 and peptide YY(3-36) on food intake and gastric emptying in rats

Ghrelin stimulates, while glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) [PYY(3-36)] inhibit, food intake and gastric emptying in rats. We determined the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake in freely feeding rats, and on the inhibitory effects of intravenous infusion of GLP-1 and PYY(3-36) on food intake and gastric emptying. Ghrelin (150 pmol x kg(-1) x min(-1)) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol x kg(-1) x min(-1) had no effect. GLP-1 (15 pmol x kg(-1) x min(-1)) inhibited food intake by 35-54%; coinfusion of ghrelin at 50 and 150 pmol x kg(-1) x min(-1) attenuated this effect by 60 and 64%, respectively. PYY(3-36) (15 pmol x kg(-1) x min(-1)) inhibited food intake by 32%; ghrelin at 15 and 50 pmol x kg(-1) x min(-1) attenuated this effect by 54 and 74%, respectively. A 20-min intravenous infusion of ghrelin (15-150 pmol x kg(-1) x min(-1)) attenuated GLP-1-and PYY(3-36)-induced inhibition of gastric emptying of saline by 6-29%. Thus, intravenous infusion of ghrelin during the early dark period stimulates food intake in freely feeding rats by increasing meal frequency, and similar doses of ghrelin attenuate gastric emptying and feeding responses to GLP-1 and PYY(3-36). These results suggest that ghrelin may stimulate food intake in part by attenuating the inhibitory effects of GLP-1 and PYY(3-36) on gastric emptying and food intake.     

Effects of Intragastric Balloon on Gastric Emptying and Plasma Ghrelin Levels in Non-morbid Obese Patients

Background: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying and ghrelin secretion in non-morbid obese patients. Patients and Methods: 17 patients were included in the study, with mean BMI of 34.4 (range 30.1–40.0). The balloon was inserted under general anaesthesia and endoscopic control, inflated with 600 ml saline, and removed 6 months later. Body weight and gastric emptying (¹³ C-octanoic acid breath test) were monitored while the balloon was in place and 1 month after removal. Ghrelin levels were measured just before balloon insertion and removal. Results: Mean weight loss was 8.7 kg (range 0–21). Gastric emptying rates were significantly decreased with the balloon in place, and returned to pre-implantation values after balloon removal. Plasma ghrelin levels were significantly decreased (95% CI: −3.8 to −20.7 ng/ml), despite concomitant weight loss. Weight reduction was not correlated to the effect of the balloon on gastric emptying, but was significantly correlated to the ghrelin variations (r=0.668, 95% CI: 0.212–0.885). Conclusions: Gastric emptying rates and plasma ghrelin levels are decreased in the presence of intragastric balloon. Weight loss induced by the intragastric balloon is related to ghrelin variations, but not to gastric emptying. Ghrelin inhibition may explain part of the effect of the balloon on satiety.     

Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells

Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates the release of growth hormone at the hypothalamus and pituitary level. Although GHS-Rs are expressed in a variety of peripheral tissues, little is known about its effect on bone independent of GH/IGF-1 axis. This study was undertaken to investigate whether ghrelin exerts a direct effect on osteoblasts. We identified mRNA and protein expression of GHS-R in primary osteoblasts as well as a number of osteoblastic cell lines, including MC3T3-E1, ROS 17/2.8, UMR-106, MG63, and SaOS2 cells. Treatment of ghrelin (10(-11) to 10(-7) M) to MC3T3-E1 cells showed dose-dependent stimulation of proliferation, which was abrogated by treatment with [d-Lys]-GHRP-6 (10(-3) M), a selective antagonist of the ghrelin receptor. Ghrelin activated ERK1/2 MAPK and pretreatment with MAPK kinase inhibitors, PD98059 attenuated the ghrelin-induced cell proliferation. Ghrelin also inhibited TNFalpha-induced apoptosis and suppressed caspase-3 activation that occurs in response to TNFalpha as well as during in vitro differentiation process. Moreover, ghrelin treatment enhanced in vitro osteoblast differentiation as evidenced by matrix mineralization, alkaline phosphatase activity, and osteoblast-specific gene expression. These results suggest that ghrelin promotes proliferation and differentiation and inhibits apoptosis of osteoblasts.     

Incretin dysfunction and hyperglycemia in cystic fibrosis: Role of acyl-ghrelin

BackgroundInsulin secretion is insufficient in cystic fibrosis (CF), even before diabetes is present, though the mechanisms involved remain unclear. Acyl-ghrelin (AG) can diminish insulin secretion and is elevated in humans with CF.MethodsWe tested the hypothesis that elevated AG contributes to reduced insulin secretion and hyperglycemia in CF ferrets.ResultsFasting AG was elevated in CF versus non-CF ferrets. Similar to its effects in other species, AG administration in non-CF ferrets acutely reduced insulin, increased growth hormone, and induced hyperglycemia. During oral glucose tolerance testing, non-CF ferrets had responsive insulin, glucagon like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels and maintained normal glucose levels, whereas CF ferrets had insufficient responses and became hyperglycemic. Interestingly in wild-type ferrets, the acyl-ghrelin receptor antagonist [D-Lys3]-GHRP-6 impaired glucose tolerance, and abolished insulin, GLP-1, and GIP responses during glucose tolerance testing. By contrast, in CF ferrets [D-Lys3]-GHRP-6 improved glucose tolerance, enhanced the insulin-to-glucose ratio, but did not impact the already low GLP-1 and GIP levels.ConclusionsThese results suggest a mechanism by which elevated AG contributes to CF hyperglycemia through inhibition of insulin secretion, an effect magnified by low GLP-1 and GIP. Interventions that lower ghrelin, ghrelin action, and/or raise GLP-1 or GIP might improve glycemia in CF.     

Combined estrogen and ghrelin administration decreases expression of p27<Superscript>kip1</Superscript> and proportion of isomyosin type I in the striated urethral and anal sphincters and levator ani of old ovariectomized rats

We compared estrogen and/or ghrelin effects on pelvic floor muscles in old versus young adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-beta estradiol (10 mug kg(-1)), ghrelin (2 mug kg(-1)), both, or vehicle (n = 6 x 4/group). Cytoplasmic p27(kip1) expression and isomyosin I proportion in striated urethral and anal sphincters and levator ani were measured, respectively, by Western blot analysis and gel electrophoresis with immunohistochemistry of muscle ghrelin receptors and radioimmunoassay of circulating growth hormone. In young adult rats, estrogen significantly decreased cytoplasmic p27(kip1) and isomyosin I signal intensities. In old rats, ghrelin and estrogen/ghrelin significantly decreased both intensities with greater estrogen/ghrelin effect. Ghrelin receptors were not immunostained in any muscle. Estrogen and/or ghrelin significantly increased or decreased, respectively, circulating growth hormone in old and young adult rats. Estrogen/ghrelin administration reversed pelvic floor muscle ageing changes in old ovariectomized rats through growth hormone production.     

Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin

The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another. When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action. This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]). For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats. In the arcuate nuclei of the Zucker fatty rat and in fasted rats, GHS-R expression is significantly increased. A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats. Ghrelin significantly increased GHS-R expression but not in dwarf rats. These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.