Growth Hormone Secretagogue Receptor Ghrelin Research Articles

Hepatic transcriptome analysis provides new insights into ghrelin regulation of the liver in Nile tilapia (Oreochromis niloticus).

Ghrelin is a growth-promoting hormone produced by the gastrointestinal tract that plays a crucial role through the ghrelin-growth hormone secretagogue receptor (GHS-R) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. To explore the effect of ghrelin on the transcriptomic profile of tilapia liver, the hepatic transcriptome of tilapia was sequenced for two groups, including saline-injected control (CL) and ghrelin-injected (GL; 2 μg/g body weight) tilapia. The transcriptome of livers from the two groups was sequenced using an Illumina HiSeqTM 2000 platform and yielded approximately 310.53 million raw reads. Subsequently, approximately 308.51 million clean reads were obtained from the total raw reads using in-house Perl scripts. Approximately 92.36% clean reads were mapped to the Nile tilapia genome using RSEM. Using the DESeq package, 250 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment of two pathways related to RNA transcription (ribosome biogenesis in eukaryotes pathway and RNA transport pathway), with a total of 14 functional DEGs. ATP-binding and muscle contraction terms were identified as enriched using Gene Ontology (GO), yielding a total of 28 DEGs. Finally, real-time quantitative PCR (RT-qPCR) was used to confirm the accuracy of the transcriptomic results. The results of RT-qPCR were highly consistent with the RNA-seq, indicating that results of RNA-seq were valid. The differences in gene expression between the groups indicated that ghrelin-injection altered energy metabolism and RNA transcription in the tilapia liver, which provides new information to help promote the growth of tilapia.

Differential expression of ghrelin and GHSR via the mTOR pathway during the dynamic carcinogenic process involving oral, potentially malignant disorders.

The purpose was to explore the sequence changes in ghrelin and GHSR in the mTOR signaling pathway during carcinogenesis involving oral, potentially malignant disorders (OPMD). The samples were confirmed through in vivo pathologic tissue screening and diagnosis. The immunohistochemical method was used to detect the expression of the ghrelin/growth hormone secretagogue receptor (GHSR) protein. The expression of ghrelin, GHSR 1α, GHSR 1β, and mammalian target of rapamycin (mTOR) RNA were detected by real-time PCR. The expression of ghrelin, GHSR, mTOR, and phosphorylated mTOR (phosphor-mTOR) protein were detected by Western blot. The expression of ghrelin/GHSR increased gradually in the dynamic process of OPMD carcinogenesis. There was a correlation between the increase in ghrelin, GHSR, mTOR, and phospho-mTOR. The in vivo expression of ghrelin/GHSR protein was the most apparent pathologic change from normal-to-mild, moderate, and severe dysplasia, and finally to the dynamic process from normal-to-mild-to-moderate dysplasia. The in vitro cell experiments based on QPCR results also proved that GHSR 1a functional receptor of ghrelin had a peak expression in LEUK-1 cells. In conclusioin, the close relationship between ghrelin and OPMD carcinogenesis can be used as a new biological target to assess the carcinogenesis of OPMD.

Estradiol and testosterone modulate the tissue-specific expression of ghrelin, ghs-r, goat and nucb2 in goldfish

Ghrelin, and nesfatin-1 (encoded by nucleobindin2/nucb2) are two metabolic peptides with multiple biological effects in vertebrates. While sex steroids are known to regulate endogenous ghrelin and NUCB2 in mammals, such actions by steroids in fish remain unknown. This study aimed to determine whether estradiol (E2) and testosterone (T) affects the expression of preproghrelin, ghrelin/growth hormone secretagogue receptor (GHS-R), ghrelin O-acyl transferase (GOAT) and NUCB2 in goldfish (Carassius auratus). First, a dose–response assay was performed in which fish were intraperitoneally (ip) implanted with pellets containing 25, 50 or 100μg/g body weight (BW) of E2 or T. It was found that sex steroids (100μg/g BW) administered for 2.5days achieved the highest E2 or T in circulation. In a second experiment, fish were ip implanted with pellets containing 100μg/g BW of E2, T or without hormone (control). RT-qPCR analyses at 2.5days post-administration show that gut preproghrelin and GOAT expression was upregulated by both E2 and T treatments, while the same effect was observed for GHS-R only in the pituitary. Both treatments also reduced hypothalamic preproghrelin mRNA expression. NUCB2 expression was increased in the forebrain of T treated group and reduced in the gut and pituitary under both treatments. These results show for the first time a modulation of preproghrelin and nucb2/nesfatin-1 by sex steroids in fish. The interaction between sex steroids and genes implicated in both metabolism and reproduction might help meeting the reproduction dependent energy demands in fish.

A relationship between motilin and growth hormone secretagogue receptors

The motilin receptor (MR) belongs to a family of Class I G protein-coupled receptors that also includes growth hormone secretagogue receptor (GHSR). Their potentially unique structure and the molecular basis of their binding and activation are not yet clear. We previously reported that the perimembranous residues in the predicted extracellular loops and amino-terminal tail of the MR were important for responses to the natural peptide ligand, motilin, and the transmembrane domains of the MR were important for a non-peptidyl ligand, erythromycin. We also reported that the perimembranous residues in the second extracellular loop of the GHSR were critical for natural ligand ghrelin binding and activity. The MR is 52% identical to GHSR, with 86% sequence identity in the transmembrane domains. In the current work, to gain insight into a relationship between MR and GHSR, we studied functional responses to motilin, erythromycin and ghrelin of expression cells of chimeric constructs of MR and GHSR and co-expression cells of both MR and GHSR. We also generated human MR transgenic mice, and clarified a relationship between motilin and ghrelin. MR(1–62)/GHSR(68–366) construct responded only to ghrelin, MR(1–102)/GHSR(108–366) responded to ghrelin and erythromycin, and MR(1–129)/GHSR(135–366) and MR(1–178)/GHSR(184–366) responded to erythromycin, while GHSR(1–183)/MR(179–412) responded to neither motilin, erythromycin nor ghrelin. MR and GHSR co-expression cells have no additional responses to these ligands. Motilin or erythromycin administration to human MR transgenic mice resulted in a decrease of serum acyl-ghrelin levels, while MR and GHSR mRNA expression in the gastrointestinal tracts were not changed. These data suggested that in species expressing both motilin–MR and ghrelin–GHSR, there is a compensatory relationship in vivo.

No Relationship between Plasma Desacyl-Ghrelin Levels and Rabeprazole-Related Delay in Gastric Emptying

Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

Expression of Growth Hormone Secretagogue Receptor on Growth Hormone-releasing Hormone Neurons and Neuropeptide Y Neurons in the Arcuate Nucleus of Rat Hypothalamus

Ghrelin is an endogenous ligand for growth hormone secretagogue (GHS) receptor (GHSR) in stomach extract. GHSs and ghrelin stimulate growth hormone (GH) secretion and food intake. In the hypothalamus, GHSR mRNA is expressed in GH-releasing hormone (GHRH) neurons and neuropeptide Y (NPY) neurons of the arcuate nucleus, which are involved in the regulatory mechanism of GH secretion and feeding behavior, respectively. We performed double-labeled immunofluorescence for GHSR and GHRH or NPY to verify the presence of GHSR protein in GHRH and NPY neurons of the arcuate nucleus. GHSR protein was found in GHRH neurons in the ventral and lateral parts of the arcuate nucleus and in NPY neurons in the portion medial to that of the GHRH neurons. These results suggest that ghrelin GHSR is involved in the regulatory mechanism of GH secretion and feeding behavior through GHRH and NPY neurons, respectively.