Ghrelin: structure and function

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.     

Quorum-sensing inhibitors as anti-pathogenic drugs

Quorum-sensing (QS) signalling systems of pathogens are central regulators for the expression of virulence factors and represent highly attractive targets for the development of novel therapeutics. In Pseudomonas aeruginosa, QS systems are also involved in elevated antibiotic tolerance of biofilms as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been identified. Promising QSI compounds have been shown to make biofilms more susceptible to antimicrobial treatments, and are capable of reducing mortality and virulence as well as promoting clearance of bacteria in experimental animal models of infection.     

Response of leaf-associated bacterial communities to primary acyl-homoserine lactone in the tobacco phyllosphere

The phyllosphere is inhabited by large populations of epiphytic bacteria that are able to modulate their phenotypes and behavior by quorum sensing (QS). However, the impact of acyl-homoserine lactones (AHLs) involved in QS on the ecology of bacteria in their natural habitat remains unclear. Therefore, we used a bioassay and liquid chromatography-mass spectrometry to detect AHLs in the tobacco phyllosphere. Our results identified several AHLs in the tobacco phyllosphere, the majority of which were short-chain AHLs. Furthermore, the addition of an exogenous N-(3-oxohexanoyl) homoserine lactone (3OC6HSL), which is seen in the naturally occurring tobacco phyllosphere, generated variability in the composition of the bacterial community as determined by denaturing gradient gel electrophoresis (DGGE) analysis and phospholipid fatty acid (PLFA) analysis. Notably, the ratio of Gram-positive (GP) bacteria increased in response to treatment with 1 μM AHL, but decreased incipiently when treated with 10 μM AHL. These observations provide insight into the composition of the leaf-colonizing epiphyte community responsible for AHLs, particularly GP bacteria as they do not use AHLs as signaling molecules for QS.     

Ghrelin的发现及研究进展

Ｇｈｒｅｌｉｎ是一个新发现的由 2 8个氨基酸组成内源性肽 ,它可与生长素促泌物受体 (ｇｒｏｗｔｈｈｏｒｍｏｎｅｓｅｃｒｅｔａｇｏｇｕｅｒｅｃｅｐｔｏｒ,ＧＨＳＲ)结合促进生长素 (ｇｒｏｗｔｈｈｏｒｍｏｎｅ ,ＧＨ)分泌。Ｇｈｒｅｌｉｎ是目前为止除了生长素释放激素 (ｇｒｏｗｔｈｈｏｒｍｏｎｅｒｅｌｅａｓｉｎｇｈｏｒｍｏｎｅ ,ＧＨＲＨ)和生长抑素 (ｓｏｍａｔｏｓｔａｔｉｎ ,ＳＳ)外 ,第三个调节腺垂体ＧＨ分泌的内源性物质。根据对目前已积累的 90多篇研究资料来分析 ,ｇｈｒｅｌｉｎ除调节ＧＨ分泌外 ,对其它器官系统也具…     

Rice and bean AHL-mimic quorum-sensing signals specifically interfere with the capacity to form biofilms by plant-associated bacteria

Many bacteria regulate their gene expression in response to changes in their population density in a process called quorum sensing (QS), which involves communication between cells mediated by small diffusible signal molecules termed autoinducers. n-acyl-homoserine-lactones (AHLs) are the most common autoinducers in proteobacteria. QS-regulated genes are involved in complex interactions between bacteria of the same or different species and even with some eukaryotic organisms. Eukaryotes, including plants, can interfere with bacterial QS systems by synthesizing molecules that interfere with bacterial QS systems.In this work, the presence of AHL-mimic QS molecules in diverse Oryza sativa (rice) and Phaseolus vulgaris (bean) plant-samples were detected employing three biosensor strains. A more intensive analysis using biosensors carrying the lactonase enzyme showed that bean and rice seed-extract contain molecules that lack the typical lactone ring of AHLs. Interestingly, these molecules specifically alter the QS-regulated biofilm formation of two plant-associated bacteria, Sinorhizobium fredii SMH12 and Pantoea ananatis AMG501, suggesting that plants are able to enhance or to inhibit the bacterial QS systems depending on the bacterial strain. Further studies would contribute to a better understanding of plant–bacteria relationships at the molecular level.     

Ghrelin stimulates growth hormone secretion and food intake in aged rats

Age-related decreases in energy expenditure have been associated with the loss of skeletal muscle and decline of food intake, possibly through a mechanism involving changes of growth hormone (GH) secretion and feeding behavior. Age-related declines of growth hormone secretion and food intake have been termed the somatopause and anorexia of ageing, respectively. Ghrelin, a 28-amino-acid peptide, was isolated from human and rat stomachs as an endogenous ligand of growth hormone secretagogue receptor. Ghrelin stimulates growth hormone release and food intake when peripherally administered to rodents and humans. Here, we investigate the relationship between age-related decline of growth hormone secretion and/or food intake and ghrelin function. Ghrelin (10 nmol/kg body weight) was administered intravenously to male 3-, 12-, 24-and 27-month-old Long-Evans rats, after which growth hormone concentrations and 2 h food intake were measured. An intravenous administration of ghrelin to rats increased food intake in all generations. In addition, to orexigenic effect by ghrelin, intravenous administration of ghrelin elicited a marked increase in plasma GH levels, with the peak occurring 15 min after administration. These findings suggest that the aged rats maintain the reactivity to administered exogenous ghrelin.     

Occurrence of diversified N‐acyl homoserine lactone mediated biofilm‐forming bacteria in rice rhizoplane

Quorum sensing (QS)‐mediated biofilm‐forming rhizobacteria are indispensable due to their competitiveness in the crop rhizosphere. In the present work, we have reported on the occurrence of diversified bacterial species capable of producing N‐acyl homoserine lactone (AHL) as the QS signal in the roots of a rice plant grown under field conditions. The AHL‐producing bacteria were directly isolated from the rice root by the biosensor reporter (Chromobacterium violaceum CV026) overlay method and characterized for biofilm production by the microtiter plate method. A total of 48 QS‐positive bacterial isolates were purified from different aged (7, 20, 24, 26, and 36 days) rice seedlings. The in vitro biofilm production and genetic diversity as revealed by BOX‐PCR fingerprinting showed high variability among the isolates. Most of the best biofilm‐forming isolates produced a N‐butyryl dl ‐homoserine lactone (a C4‐AHL type) signal in the medium. The 16S ribosomal RNA (rRNA) gene sequence of these putative elite isolates identified that they were close to Aeromonas hydrophila (QS7‐4; QS36‐2), A. enteropelongenes (QS20‐8), A. veronii (QS36‐3), Enterobacter sp. (QS20‐11), Klebsiella pneumoniae (QS24‐6), Kosakonia cowanii (QS24‐21), Providentia rettigeri (QS24‐2), Sphingomonas aquatilis (QS24‐17), and Pseudomonas sihuiensis (QS24‐20). These strains profusely colonized the rice root upon inoculation and formed biofilms on the surface of the root under gnotobiotic conditions. Developing inoculants from these strains would ensure competitive colonization on the rhizoplane of the crop through their biofilm and thereby improve plant growth and health.     

Effects of bacterial N-acyl homoserine lactones on human Jurkat T lymphocytes-OdDHL induces apoptosis via the mitochondrial pathway

Diverse Gram-negative bacteria communicate with each other by using diffusible N-acyl-homoserine lactone (AHL) signaling molecules to coordinate gene expression with cell population density. This mechanism termed ‘quorum sensing’ is involved in the regulation of physiological functions as well as multiple virulence determinants. It becomes more and more evident, that bacteria communicate not only with each other but also with their host. Up to now, little is known about this interkingdom communication. The AHL quorum sensing molecule N-3-(oxododecanoyl)-l-homoserine lactone (OdDHL) from Pseudomonas aeruginosa has been shown to influence the immune system of the host. The role and potential influence of other AHL molecules from other bacteria have so far not been determined. In this paper, we investigated the role of 7 different AHLs on apoptosis of human Jurkat T lymphocytes. We found, that among all homoserine lactones tested, only OdDHL rapidly induced apoptosis which was accompanied by the breakdown of the mitochondrial transmembrane potential (ΔΨ_m). Since overexpression of anti-apoptotic Bcl-2 completely abrogated the apoptotic effect, we presume that OdDHL induces apoptosis by activation of the intrinsic mitochondrial apoptosis pathway. The reason that bacteria induce apoptosis is largely unknown. We suspect that through apoptosis an anti-inflammatory response is triggered.     

Acyl Homoserine Lactones Induce Early Response in the Airway

Acyl homoserine lactones (AHLs) are intercellular signaling molecules used in quorum sensing by Gram‐negative bacteria. We studied the early effects on the rat airway of in vivo intratracheal administration of AHLs (i.e., P. aeruginosa and B. cepacia) to test the hypothesis that AHLs also act on the airway cells, modifying secretory mechanisms which are important in mucosal defense. One hour after treatment, N‐butyryl‐homoserine lactone (C4‐HL) had caused dilated extracellular spaces, loss of cilia, reduction of secretory material, and the presence of prenecrotic elements in the epithelium, while N‐octanoyl‐homoserine lactone (C8‐HL) caused a mild lesion in the epithelium. After treatment with either C4‐ or C8‐HL, reduced immunoreactivity was found using CC10 antibody. At ultrastructural examination, dilatation of the mitochondria was evident in ciliate and secretory cells, while solitary chemosensory cells appeared better preserved, showing aspects of nucleocytoplasmic activation. Using microarray analysis, we found down‐regulation of early gene Fos and Egr1 in all AHL‐treated specimens. In vivo pharmacological magnetic resonance imaging after C4‐ or C8‐HL treatment showed a slight increase in tracheal secretion at a first evaluation 5 min after administration, with no increase in the following minutes. In conclusion, AHLs induce an early mucosal response, and the chondriomas of ciliate and secretory cells are the main cytological target of AHL action. Our results show that AHL action is not limited to activation of conspecific bacteria, but also modifies innate airway defense mechanisms. Anat Rec, 292:439–448, 2009. © 2009 Wiley‐Liss, Inc.     

Alterations in stomach ghrelin production and in ghrelin-induced growth hormone secretion in the aged rat

Ghrelin is a recently discovered stomach hormone that stimulates growth hormone (GH) secretion, food intake, adiposity, and growth. In this report, we present new and previously published data from our laboratory showing that stomach ghrelin production and secretion are increased, and that GH release in response to exogenous ghrelin is enhanced in the aged rat. Together, these data suggest that the aging associated decline in GH secretion is not due to a reduction in stomach ghrelin secretion or a stimulatory action on GH release.     

The role of ghrelin in energy homeostasis and its potential clinical relevance (Review)

The novel gastric hormone ghrelin, a 28-amino acid peptide, has been identified as a potent growth-hormone secretagogue. Ghrelin production is regulated by nutritional and hormonal factors. Besides stimulating growth hormone secretion, studies show that ghrelin exerts a number of central and peripheral actions such as the regulation of food intake, the control of energy balance, glucose metabolism and insulin release, cardiovascular actions, the stimulation of gastric acid secretion, and motility. The broad spectrum of biological activities associated with ghrelin continues to expand. In the future, the diverse functions of ghrelin raise the possibility of its clinical application in a large number of pathological conditions.     

Isolation and characterization of quorum‐sensing signalling molecules in Pseudomonas aeruginosa isolates recovered from nosocomial infections

Pseudomonas aeruginosa is one of the most common pathogens in nosocomial infections. Many studies have documented the role of quorum‐sensing (QS) systems in antibiotic tolerance of P. aeruginosa. N‐acyl homoserine lactones (AHLs) serve as QS signalling molecules and can be a target for modulating bacterial pathogenicity. In this study, nosocomial isolates of P. aeruginosa were characterized for the presence of different types of QS signalling molecules. AHLs were solvent extracted and quantified by determination of β‐galactosidase activity using the Escherichia coli MG4 reporter strain. Further characterization was performed by analytical thin layer chromatography coupled with detection using the Agrobacterium tumefaciens A136 biosensor strain. All P. aeruginosa isolates produced AHLs, but there were differences in the quantity and nature of AHLs. We identified AHLs belonging to C4‐homoserine lactone (HSL), C6‐HSL, C8‐HSL, C10‐HSL and C12‐HSL. AHL profiling of P. aeruginosa isolates showed differences in the amounts and types of AHLs, suggesting differences in the virulence factors and the potential for infection. Our results may be investigated further using animal model systems.     

Bacterial communications in implant infections: a target for an intelligence war

The status of population density is communicated among bacteria by specific secreted molecules, called pheromones or autoinducers, and the control mechanism is called "quorum-sensing". Quorum-sensing systems regulate the expression of a panel of genes, allowing bacteria to adapt to modified environmental conditions at a high density of population. The two known different quorum systems are described as the LuxR-LuxI system in gram-negative bacteria, which uses an N-acyl-homoserine lactone (AHL) as signal, and the agr system in gram-positive bacteria, which uses a peptide-tiolactone as signal and the RNAIII as effector molecules. Both in gram-negative and in gram-positive bacteria, quorum-sensing systems regulate the expression of adhesion mechanisms (biofilm and adhesins) and virulence factors (toxins and exoenzymes) depending on population cell density. In gram-negative Pseudomonas aeruginosa, analogs of signaling molecules such as furanone analogs, are effective in attenuating bacterial virulence and controlling bacterial infections. In grampositive Staphylococcus aureus, the quorum-sensing RNAIII-inhibiting peptide (RIP), tested in vitro and in animal infection models, has been proved to inhibit virulence and prevent infections. Attenuation of bacterial virulence by quorum-sensing inhibitors, rather than by bactericidal or bacteriostatic drugs, is a highly attractive concept because these antibacterial agents are less likely to induce the development of bacterial resistance.     

Effects of ghrelin on some plasma hormonal changes in juvenile Persian sturgeon (Acipenser persicus)

The functions of ghrelin, a novel weight-regulatory peptide, have not been intensively investigated in primitive fish. This experiment was conducted to determine whether ghrelin has a specific effect on growth hormone (GH), prolactin and cortisol levels in Persian sturgeon (Acipenser persicus). Juvenile Persian sturgeons with a mean body weight of 320?±?30?g were given a single injection of ghrelin at three doses of 0.1, 1 and 10?ng/g body weight. Control animals were injected with vehicle (sterile saline) only. Blood samples were collected at 0, 2, 4, 8, 24, 48 and 72?h after injection. The level of plasma hormones were determined by ELISA kit. As expected, ghrelin injection significantly elevated plasma GH (P?<?0.05), whereas prolactin levels did not significantly change after injection (P?>?0.05). Plasma cortisol levels decreased in fish injected with high doses of ghrelin (P?<?0.05). Ghrelin at 10?ng/g body weight had the most influence on GH release, and 1?ng/g ghrelin injection caused the lowest level of cortisol. These results show for the first time that ghrelin induces some plasma hormonal changes in sturgeon fish, as lower vertebrates, but more investigations are needed in this area.     

N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa

In gram-negative bacterial pathogens, such as Pseudomonas aeruginosa and Yersinia pseudotuberculosis, cell-to-cell communication via the N-acylhomoserine lactone (AHL) signal molecules is involved in the cell population density-dependent control of genes associated with virulence. This phenomenon, termed quorum sensing, relies upon the accumulation of AHLs to a threshold concentration at which target structural genes are activated. By using biosensors capable of detecting a range of AHLs we observed that, in cultures of Y. pseudotuberculosis and P. aeruginosa, AHLs accumulate during the exponential phase but largely disappear during the stationary phase. When added to late-stationary-phase, cell-free culture supernatants of the respective pathogen, the major P. aeruginosa [N-butanoylhomoserine lactone (C4-HSL) and N-(3-oxododecanoyl)homoserine lactone (3-oxo-C12-HSL)] and Y. pseudotuberculosis [N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL)] AHLs were inactivated. Short-acyl-chain compounds (e.g., C4-HSL) were turned over more extensively than long-chain molecules (e.g., 3-oxo-C12-HSL). Little AHL inactivation occurred with cell extracts, and no evidence for inactivation by specific enzymes was apparent. This AHL turnover was discovered to be due to pH-dependent lactonolysis. By acidifying the growth media to pH 2.0, lactonolysis could be reversed. By using carbon-13 nuclear magnetic resonance spectroscopy, we found that the ring opening of homoserine lactone (HSL), N-propionyl HSL (C3-HSL), and C4-HSL increased as pH increased but diminished as the N-acyl chain was lengthened. At low pH levels, the lactone rings closed but not via a simple reversal of the ring opening reaction mechanism. Ring opening of C4-HSL, C6-HSL, 3-oxo-C6-HSL, and N-octanoylhomoserine lactone (C8-HSL), as determined by the reduction of pH in aqueous solutions with time, was also less rapid for AHLs with more electron-donating longer side chains. Raising the temperature from 22 to 37 degrees C increased the rate of ring opening. Taken together, these data show that (i) to be functional under physiological conditions in mammalian tissue fluids, AHLs require an N-acyl side chain of at least four carbons in length and (ii) that the longer the acyl side chain the more stable the AHL signal molecule.     

Ghrelin effects on gonadotropin secretion in male and female rats

Ghrelin is a 28-amino acid peptide primarily involved in the control of food intake and growth hormone secretion. The present experiments were carried out to analyze the potential involvement of ghrelin in the control of gonadotropin secretion. Prepubertal intact and gonadectomized female and male rats, cyclic rats in diestrus, lactating rats and aged female rats were i.c.v. injected with ghrelin (3 nmol/rat) and blood samples were obtained by decapitation 15 min later. In addition, we analyzed the effects of ghrelin on in vitro basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin secretion. Our present results indicate that ghrelin inhibited luteinizing hormone (LH) secretion in vivo in prepubertal males as well as gonadectomized males and females, whereas follicle-stimulating hormone (FSH) remained unaffected. In vitro, ghrelin stimulated the secretion of both gonadotropins, and differentially modulated the response to LHRH; the LH response was inhibited, while the FSH response was enhanced. Overall, our current data open up the possibility that ghrelin may be involved in the control of LH secretion, and in the dissociation of both gonadotropins that takes place in many physiological, pathological and experimental situations.     

生长素释放肽的发现、发展及展望

生长素释放肽（Growth hormone-releasing peptides,GHRP)于70年代末、80年代初依据蛋氨酸－亮氨酸脑啡肽（met-enkephalin）的结构首次合成。以后又合成了数种类型的GHRP，其结构已远不同于met-enkephalin的结构。但均可强烈刺激生长素（growth hormone,GH）分泌。由于1982年下丘脑生长素释放激素的发现，GHRP研究在80年代进展不大。在90年代，由于制药界的努力和驱动，GHRP研究进展较快，非肽类生长素释放刺激剂（non-peptide GH secretagogues）于1994年首次合成，第一个GHRP受体也于1996年首次克隆成功。1999年从胃内分泌细胞首次发现可能的内源性GHRP,命名为ghrelin。Glrelin可激动GHRP受体并刺激GH分泌。最近几年，GHRP对生长素轴以外的外周组织的作用有诸多报道。GHRP的这些外周作用包括对心血管功能、摄食、脂肪细胞分化、胃酸分泌和胃肠运动的调节等。     

GH-related and extra-endocrine actions of GH secretagogues in aging

Growth hormone (GH) secretion declines with aging in mammals, including humans. Defective pituitary function does not play a major role in this event. Rather, age-related changes involving the function of specific hypothalamic peptides for GH regulation, GH-releasing hormone (GHRH) and somatostatin (SS), appear to be the fundamental factors. Experimental evidence indicates that GHRH synthesis is impaired with aging in the rat hypothalamus, and that a relative hyperfunction of the SS-ergic system is present. In the elderly, systemic, short-term administration of GHRH enhances GH secretion and increases the formation of the GH-dependent peptide IGF-1. In old dogs, a combination of GHRH and clonidine (CLO), an alpha(2)-adrenoceptor agonist, reportedly acting via GHRH stimulation and SS inhibition, is the most effective stimulus to rejuvenate the apulsatile GH secretion. Discovery of GH secretagogues (GHSs), a series of peptydil and non-peptydil synthetic molecules endowed with a strong GH-releasing activity, the cloning of a GHS receptor (GHS-R), present in the hypothalamus and the pituitary, the isolation of the endogenous ligand of GHS-R, ghrelin, a 28-amino acid peptide whose main source is the stomach, pose the issue for the physiologic role of the GHS/ghrelin system and forces revision of our current understanding of GH regulation in different GH deficiency (GHD) states, including aging. GHSs are very effective for enhancing GH secretion in old subjects, but long-term studies are needed to assess their safety and the real biological impact of GHS replacement therapy in aging. Therapeutic use of GHSs can also be envisaged to restore, via GH-independent mechanisms, functional, and structural age-related alterations, such as anorexia, sexual dysfunction, cardiovascular damage, bone loss.     

Nocturnal ghrelin levels--relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol--and gender differences

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue receptor, stimulates sleep, appetite and weight gain as well as the secretion of GH, adrenocorticotropic hormone (ACTH), cortisol in humans and rodents. The interaction between nocturnal ghrelin levels, sleep EEG and the secretion of these hormones was not investigated systematically so far. Furthermore conflicting data exist on gender differences in nocturnal ghrelin secretion. We examined simultaneously sleep EEG and the nocturnal levels of ghrelin, GH, ACTH and cortisol in young and middle-aged normal human subjects (eight males, eight females). A significant interaction between gender and the course of ghrelin concentration was observed to the interval between 20:00 and 23:00 hours. In males a continuous increase of ghrelin levels before sleep onset was found. In females, however, a rise of ghrelin during the night was missed. We found a trend suggesting a lower time spent in stage I sleep in subjects with high nocturnal ghrelin levels. Other systematic interactions between plasma ghrelin, sleep EEG and other hormones were not found. No peak in plasma ghrelin levels resembling the GH surge was observed. We suggest that under naturalistic conditions plasma ghrelin levels show no distinct interaction with sleep.     

Ghrelin活化人T细胞翻译起始分子通过mTOR信号转导通路

目的:探讨Ghrelin活化人T细胞翻译起始分子的信号转导机理。方法:采用微柱法分离人外周血T细胞,采用Western blot方法检测mTOR信号通路分子和蛋白质翻译调控分子的磷酸化状态和含量。采用mTOR抑制剂:雷帕霉素,PI3KⅠ抑制剂:LY294002,PI3KⅢ抑制剂:3-甲基腺嘌呤,Ghrelin拮抗剂:Des-Lys-3-GHRP6和AKT抑制剂:A443654和Ghrelin研究相应信号通路。结果:①人T细胞表面有Ghrelin受体(GHSR1a)表达。②Ghrelin与GHSR1a结合后可活化mTOR。③Ghrelin磷酸化两个mTOR下游靶分子4E-BP-1和P70 S6K,P70 S6K进一步磷酸化核糖体S6蛋白。④Ghrelin磷酸化蛋白质翻译起始帽子结构的两个重要分子eIF4E和eIF4G。结论:Ghrelin促进人T细胞mRNA翻译起始的机理是活化mTOR信号转导通路。