首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 46 毫秒
1.
生长激素和生长激素受体的多样性   总被引:8,自引:0,他引:8  
李虹 《生物学杂志》2002,18(4):10-11,3
生长激素及其受体对动物生长发育起着重要的作用。转录过程选择性剪接和存在多种降解途径可能是GH或GHR产生多样性的原因。随着GH结构形态的改变,其功能也在发生变化。GH基因的多样性对鸡的抗病选择性反应与产蛋性能有相关,GH和GHR基因的多样性会影响奶牛的产奶生产性能。GHR的分子多样性可能导致动物生长发育模式的变异,例如动物的矮小病。  相似文献   

2.
生长激素促释放剂受体配体的研究进展   总被引:2,自引:0,他引:2  
生长激素促释放剂是一种合成的小分子化合物,它通过生长激素促释放剂受体而起作用,该受体是一种新的G蛋白偶联受体。以前曾认为生长激素促释放剂受体是一种孤儿受体,直到近年来从人和鼠的胃中鉴定到Ghrelin的存在,而改变了这种看法。Ghrelin是包含28个氨基酸残基的肽,在3号位的丝氨酸位点有辛酰化基团。该肽是在X/A样细胞分泌颗粒中发现的,Ghrelin的发现表明促垂体分泌生长激素可能不止受到来自下丘脑的生长激素释放激素的调节,同时还可能受到来自胃和下丘脑的Ghrelin的调节。  相似文献   

3.
生长激素受体的研究进展   总被引:10,自引:0,他引:10  
生长激素(GH)在促进动物生长、发育等代谢过程中起着重要作用,GH发挥生理作用的第一步是与靶细胞膜表面的生长激素受体(CHR)结合。现已基本阐明了CHR的结构及由CHR介导的信号转导途径,对GHR基因表达调节的机制也有了一定的了解。GHR是由约620个氨基酸组成的单链跨膜糖蛋白,其胞外区、跨膜区及胞区内分别由约245、25及350个氨基酸组成。由GHR介导的信号转导途径主要有:①酪氨酸激酶系统;②蛋白激酶C途径;③胰岛素受体底物途径。营养状况及GH等内分泌因子对GHR的表达也有调节作用。  相似文献   

4.
生长激素和生长激素受体的分子生物学   总被引:5,自引:0,他引:5  
1 .生长激素的结构生长激素 (growthhormone ,GH)一般含有 1 91个氨基酸 ,约 2 2kD。猪与牛的GH氨基酸序列具有高度的同源性 (约 90 % ) [1] 。猪和牛的GH对人没有促进生长的作用 ,可能是猪和牛GH对人的生长激素受体(growthhormonereceptor ,GHR )的结合亲和性低于人GH对人GHR的结合亲和性的缘故。GHmRNA翻译的初级产物是前生长激素 ,它比成熟GH在N端多出 2 6个氨基酸残基的疏水信号肽[2 ] 。通过X射线衍射技术等研究发现 ,GH由 4个螺旋组成 ,自N端至C端依次为螺旋 1~ …  相似文献   

5.
16头长白×大约克去势公猪, 随机分成试验组和对照组, 每天注射重组猪生长激素(rpGH, 每头每天4 mg) 或生理盐水, 28 d后采样. 用RIA法测定血清中胰岛素样生长因子1(IGF-Ⅰ)和瘦蛋白含量, 用反转录多聚酶链式反应(RT-PCR)方法, 以18S rRNA作内标, 定量分析肝脏、肌肉生长激素受体 (GHR) 和IGF-ⅠmRNA的相对丰度.结果显示: (ⅰ) 试验组平均日增重提高26.1% ( P <0.05); (ⅱ)血清IGF-Ⅰ水平提高70.94% (P<0.01), 血清瘦蛋白降低34.80%(P<0.01); (ⅲ) 肝脏GHR mRNA增加24.45% (P < 0.05), IGF-ⅠmRNA增加45.30% (P<0.01), 背最长肌GHR和IGF-Ⅰ mRNA表达无明显变化. 结果表明, 重组猪生长激素能明显提高生长猪生长性能. 上调肝脏GHR, 促进肝脏产生IGF-Ⅰ, 而对肌肉GHR和IGF-I基因表达无影响, 提示重组GH对基因表达的影响有组织特异性.  相似文献   

6.
报道了豚鼠肝生长激素受体(GHR)的cRNA克隆和编码区序列。它由1899bp组成,编码610个氨基酸。此外,还报道豚鼠GHR的结构特征和同源性比较的结果。  相似文献   

7.
黑鲷生长激素放射受体分析法的建立及其受体组织的分布   总被引:2,自引:0,他引:2  
利用黑棘鲷 (Acanthopagrusbutcheri)生长激素 (brGH )作为配体 ,建立了黑鲷 (Sparusmacrocephalus)生长激素受体放射受体分析法 (RadioreceptorAssay ,RRA)并分析其组织分布特征。在 2 5℃下 ,12 5I brGH与黑鲷肝细胞膜蛋白的特异性结合具有如下特点 :(1)时间依赖性 特异性结合达最大结合量一半的时间 (Ta1/ 2 )为 10 4h ,结合达到平衡状态需 2 0h ;激素 受体复合物的解离在 3h之内最快 ,2 4h后仅解离约40 % ,表明激素 -受体复合物的结合仅具部分可逆转性 ;(2 )可饱和性 12 5I brGH与黑鲷肝细胞膜蛋白的特异性结合随着膜蛋白浓度或12 5I brGH加入量的上升而呈逐渐上升并达到饱和状态的趋势 ;(3)可取代性 12 5I brGH与黑鲷肝细胞膜蛋白的特异性结合可被非标记brGH竞争性地取代 ,将特异性结合取代 5 0 % (ED50 )所需非标记brGH约为 3 8ng ,非标记重组金鱼生长激素 (rgfGH)及人生长激素 (hGH)对12 5IbrGH的竞争性取代能力明显较brGH低 ,而重组金鱼催乳素 (rgfPRL)、羊催乳素 (oPRL)在该系统中几乎无交叉反应。Scachard作图分析表明黑鲷肝细胞膜蛋白存在brGH单一的高亲和结合位点 ,Ka为 (3 49± 0 2 4)× 10 10 (mol/L) -1,Bmax为 146 8± 10 6fmol/mgprotein。结果表明 ,brGH与黑鲷肝细胞膜蛋白的  相似文献   

8.
大熊猫生长激素受体(GHR)cDNA的克隆与序列分析   总被引:7,自引:4,他引:7       下载免费PDF全文
根据已报道的若干物种GHR 基因cDNA 序列设计引物, 利用RT- PCR 技术首次从大熊猫肝脏组织总RNA中扩增出GHR 基因编码区全长cDNA 序列, 克隆于pGEM®-T 载体后进行测序和序列分析。结果表明,大熊猫GHR 的ORF为1 917 bp , 编码638 个氨基酸的前体蛋白, 由18 个氨基酸的信号肽和620 个氨基酸的成熟肽组成,与人、狗、猪GHR 结构相似, 大熊猫GHR 成熟肽由246 个氨基酸的胞外区、24 个氨基酸的跨膜区和350 个氨基酸的胞内区组成, 并具GHR 的特征性结构。序列相似性比较显示, 大熊猫GHR 与哺乳类GHR 具有69 %~93 %的高序列相似性, 与爬行类和鸟类的序列相似性也达到60 % , 而与鱼类的序列相似性较低, 仅为30 %左右。与其它哺乳动物GHR 相比, 大熊猫GHR 在氨基酸序列上也存在明显的特异性。  相似文献   

9.
为研究生长激素对中华鲟生长的调控机制,克隆了中华鲟生长激素受体cDNA.csGHRcDNA的可读框编码了611个氨基酸残基的跨膜蛋白质,含有GHR的所有特征结构域.序列对比发现其他种属GHR中高度保守的氨基酸残基在csGHR中发生了替换.我们利用CHO细胞分析了csGHR的生物功能和csGHR分子中高度保守性氨基酸残基替换的生物意义.csGHR稳定表达细胞中共转染的受丝氨酸蛋白酶抑制剂2.1(Spi1.2)启动子驱动的荧光素酶报告基因受海鲤生长激素(seabream GH,sbGH)诱导表达,并且sbGH诱导稳定表达细胞显著增殖.csGHR稳定表达细胞培养液中检测到中华鲟生长激素结合蛋白质,并且csGHBP的生成需要金属蛋白酶活性的参与.csGHR配体结合域的Asp突变为Glu显著提高csGHR介导的上述生物活性,而Asp突变为Ala则明显降低csGHR的生物活性.这些结果表明,克隆的csGHR具有完全生物功能,并且csGHBP可能通过csGHR蛋白酶解而生成.这些发现将有助于全面了解中华鲟生长调控机制.  相似文献   

10.
生长激素分泌促进剂及构效关系研究进展   总被引:1,自引:0,他引:1       下载免费PDF全文
生长激素分泌促进剂是一类作用于垂体和下丘脑的具有专一性促生长激素释放作用的寡肽及其类似物.由于其分子质量小、活性高、可口服、作用专一而有可能成为新的生长激素治疗药物.目前已经发展了很多具有此类活性的多种结构的化合物,如肽、环肽、肽醇及非肽类似物等.尽管这类化合物的作用机制尚未完全明确,但已有证据表明存在新的调节生长激素分泌的途径和新的调节因子.  相似文献   

11.
    
To determine mechanisms for age-related decrease of GHS-R1a expression in the chicken proventriculus, changes in mRNA expression of ghrelin and ghrelin-O-acetyltransferase (GOAT) as well as ghrelin concentrations in the proventriculus and plasma were examined in growing chickens. Changes in expression levels of ghrelin, GOAT and GHS-R1a mRNAs were also examined in different brain regions (pituitary, hypothalamus, thalamus, cerebellum, cerebral cortex, olfactory bulb, midbrain and medulla oblongata). Ghrelin concentrations in the proventriculus and plasma increased with aging and reached plateaus at 30–50 days after hatching. High level of ghrelin mRNA decreased at 3 days after hatching, and it became stable at half of the initial level. Expression levels of GHS-R1a and GOAT decreased 3 or 5 days after hatching and became stable at low levels. Significant negative correlations were found between plasma ghrelin and mRNA levels of GOAT and GHS-R1a. Expression levels of ghrelin mRNA were different in the brain regions, but a significant change was not seen with aging. GHS-R1a expression was detected in all brain regions, and age-dependent changes were observed in the pituitary and cerebellum. Different from the proventriculus, the expression of GOAT in the brain increased or did not change with aging. These results suggest that decreased GHS-R1a and GOAT mRNA expression in the proventriculus is due to endogenous ghrelin-induced down-regulation. Expression levels of ghrelin, GOAT and GHS-R1a in the brain were independently regulated from that in the proventriculus, and age-related and region-dependent regulation pattern suggests a local effect of ghrelin system in chicken brain.  相似文献   

12.
Ghrelin (GHR) is a recently discovered endocrine regulatory peptide of gastrointestinal origin with multiple functions including cardiovascular effects. However, contradictory data are available on the vascular actions of GHR in different organs and species. The aim of this study was to characterize the direct effect of the peptide on the canine coronary bed and to evaluate the role of the growth hormone secretagogue receptor (GHS-R) in the effect of GHR on coronary arterioles. The presence of GHS-R1a and 1b subtypes in canine coronary arterioles was investigated using Western blotting and immunohistochemistry. Responses of coronary arterioles with spontaneous and elevated vascular tone (the latter evoked by the thromboxane mimetic agent U46619, 10−7-10−6 mol/l) to GHR (10−9-3 × 10−7 nmol/l) were recorded by video-microscopy as changes of vessel diameter. Positive immunostaining for both GHS-R subtypes was found in the wall of intramural arterioles. The microarteriographic study results showed that GHR alone could not elicit any significant effect on vessel diameter of arterioles with spontaneous tone. However, when vascular smooth muscle was preconstricted by the thromboxane mimetic agent U46619, administration of GHR induced further constriction (+31 ± 9% increase in contraction p < 0.01). This was not abolished by the specific blockade of GHS-R1a by d-Lys3-GHRP-6 (5 × 10−6 mol/l). The results suggest that GHR induces tone-dependent constriction of canine coronary arterioles which is mediated by a receptor other than GHS-R1a.  相似文献   

13.
With one quarter of the population of the Western world now considered obese, it is essential that we understand the factors giving rise to elevated fat deposition. This review summarizes the cellular and molecular mechanisms governing the volume of white adipose tissue (WAT), and outlines the physiological signals that regulate these processes. Particular attention is given to the role of the gastric hormone, ghrelin, describing its actions in general and presenting detailed evidence of its role in regulating adipocyte biology. Combining this evidence with an analysis of the factors governing ghrelin secretion, leads to the hypothesis that during periods of food deprivation ghrelin acts as an energy deficit signal, defending the fat stored in responsive WAT against the forces of utilization. This scenario has clear implications for programmes of sustainable weight loss.  相似文献   

14.
A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-d-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-d-Ser-AIB derivative.  相似文献   

15.
We report here the ontogenic changes in mRNA expression of chicken ghrelin (cGhrelin) and its receptor (cGHS-R1a) and the effects of fasting and refeeding on cGhrelin and cGHS-R1a mRNAs expression in 30-day-old broiler chickens. The level of cGhrelin mRNA in the proventriculus was low from embryo--day 15 (E15) to E19, but dramatically increased at post-hatching-day 2 (P2), then remained constant until P30 and followed by a significant decrease at P44 when there was a diet transition at P31 and thereafter. The decreased level was reversed at P58. Hypothalamic cGhrelin mRNA and proventriculus and hepatic cGHS-R1a mRNA were significantly increased at P30. The cGhrelin mRNA level in the proventriculus significantly increased in response to either 12-h or 36-h fasting but did not decrease after subsequent 12-h refeeding. The level of cGHS-R1a mRNA in the proventriculus was significantly upregulated in response to a 12-h fast but not to a 36-h fast and returned to the control level upon 12-h refeeding. Interestingly, it was apparent that the mRNA levels of both cGhrelin and cGHS-R1a in the liver were upregulated in response to fasting in a time-dependent manner and returned to the control level with subsequent refeeding. These results suggest that the expression pattern of ghrelin and its receptor mRNAs distinctly change in tissues depending on ontogenic stages and feeding states in poultry.  相似文献   

16.
The first enantioselective synthesis of (d)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid 3 was achieved. The incorporation of the titled compound into growth hormone secretagogue (GHS) compounds resulted in new analogs 10 and 16, both of which had significantly increased in vitro potency. The compound 10 also showed improved in vivo efficacy as well as pharmacokinetic properties in rat models.  相似文献   

17.
Liu B  Garcia EA  Korbonits M 《Peptides》2011,32(11):2191-2207
Ghrelin is a 28 amino acid peptide hormone that is produced both centrally and peripherally. Regulated by the ghrelin O-acyl transferase enzyme, ghrelin exerts its action through the growth hormone secretagogue receptor, and is implicated in a diverse range of physiological processes. These implications have placed the ghrelin signaling pathway at the center of a large number of candidate gene and genome-wide studies which aim to identify the genetic basis of human heterogeneity. In this review we summarize the available data on the genetic variability of ghrelin, its receptor and its regulatory enzyme, and their association with obesity, stature, type 2 diabetes, cardiovascular disease, eating disorders, and reward seeking behavior.  相似文献   

18.
Recent studies have suggested that ghrelin plays a direct role in controlling female reproduction. The aim of the present study was to investigate the mRNA and protein expression of ghrelin and its receptor (via real time PCR, Western blot and immunohistochemistry analysis, respectively) in porcine corpora lutea (CL) collected during early (CL1: 1-2 days after ovulation), middle (CL2: 7-10 after ovulation), and late luteal phase (CL3: 13-15 after ovulation). Ghrelin expression and concentration of both acylated and unacylated forms of ghrelin significantly increased during CL development. Immunohistochemistry analysis shown localization of ghrelin protein in the cytoplasm of large luteal cells. No changes in the expression of the ghrelin receptor were observed. Direct in vitro effects of ghrelin on progesterone (P4) secretion and 3-beta-hydroxysteroid dehydrogenase (3β-honestly significant difference (HSD)) activity, which were measured by the conversion of pregnenolone (P5) to P4, and 3β-HSD protein expression were then analyzed. To assess 3β-HSD activities, mature luteal cells were first cultured for 24 h with ghrelin at 100, 250, 500 and 1000 pg/mL with P5, or with aminoglutethimide (AMG). AMG is an inhibitor of CYP11A1-mediated hydroxylation; an addition of AMG and P5 enabled P4 production to serve as an index of 3β-HSD activity. Inhibitory effects of ghrelin on P4 secretion, 3β-HSD activity and protein expression were observed. In conclusion, the presence of ghrelin and its receptor in porcine corpora lutea and the direct inhibitory effects of ghrelin on luteal P4 secretion and 3β-HSD suggest potential auto/paracrine regulation by ghrelin in the luteal phase of ovary function.  相似文献   

19.
20.
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.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号