Dataset Information

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas.

ABSTRACT: Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite-inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum of human pituitary adenoma subtypes (n=34) and in normal pituitary tissue (n=3). The mRNA and protein expression levels were quantified using a competitive reverse transcription-polymerase chain reaction and western blotting and the correlation of the results with the clinical parameters was assessed. mRNA and protein expression of ghrelin and GHSR was detected in all samples with the highest mean level in GH adenomas, a moderate level in clinically non-functioning adenomas and the lowest level in adrenocorticotropin adenomas. A significant correlation between the ghrelin and GHSR mRNA expression levels was observed in the GH adenomas (n=12) (r=0.8435, P=0.0006). The ghrelin mRNA expression level in the GH adenomas correlated positively with the basic serum GH level (n=12) (r=0.6488, P=0.0225). Furthermore, the mean level of ghrelin mRNA expression was significantly higher in invasive adenomas than in noninvasive adenomas (P<0.01). Collectively, the results of the study provided evidence that ghrelin and GHSR are expressed in the various subtypes of pituitary adenoma, with specific overexpression in GH adenomas. The study suggests that the binding of ghrelin to GHSR promotes the secretion of GH and plays an important role in the development of GH adenomas via autocrine and/or paracrine effects.

SUBMITTER: Wang J

PROVIDER: S-EPMC4471707 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas.

Wang Junwen J Guo Songbo S Han Lin L Fang Mingbo M Wang Lei L Bartsch Jörg W JW Li Jun J

Experimental and therapeutic medicine 20150311 5

Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite-inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum o ...[more]

PMID: 26136913

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Project description:The gut hormone ghrelin is involved in numerous metabolic functions, such as the stimulation of growth hormone secretion, gastric motility, and food intake. Ghrelin is modified by ghrelin O-acyltransferase (GOAT) or membrane-bound O-acyltransferase domain-containing 4 (MBOAT4) enabling action through the growth hormone secretagogue receptors (GHS-R). During the course of evolution, initially strong ligand/receptor specificities can be disrupted by genomic changes, potentially modifying physiological roles of the ligand/receptor system. Here, we investigated the coevolution of ghrelin, GOAT, and GHS-R in vertebrates. We combined similarity search, conserved synteny analyses, phylogenetic reconstructions, and protein structure comparisons to reconstruct the evolutionary history of the ghrelin system. Ghrelin remained a single-gene locus in all vertebrate species, and accordingly, a single GHS-R isoform was identified in all tetrapods. Similar patterns of the nonsynonymous (dN) and synonymous (dS) ratio (dN/dS) in the vertebrate lineage strongly suggest coevolution of the ghrelin and GHS-R genes, supporting specific functional interactions and common physiological pathways. The selection profiles do not allow confirmation as to whether ghrelin binds specifically to GOAT, but the ghrelin dN/dS patterns are more similar to those of GOAT compared to MBOAT1 and MBOAT2 isoforms. Four GHS-R isoforms were identified in teleost genomes. This diversification of GHS-R resulted from successive rounds of duplications, some of which remained specific to the teleost lineage. Coevolution signals are lost in teleosts, presumably due to the diversification of GHS-R but not the ghrelin gene. The identification of the GHS-R diversity in teleosts provides a molecular basis for comparative studies on ghrelin's physiological roles and regulation, while the comparative sequence and structure analyses will assist translational medicine to determine structure-function relationships of the ghrelin/GHS-R system.

Project description:The growth hormone secretagogue receptor (GHSR) (ghrelin receptor) plays an important role in the regulation of food intake and energy homeostasis. The GHSR gene lies on human chromosome 3q26 within a quantitative trait locus strongly linked to multiple phenotypes related to obesity and the metabolic syndrome. Because the biological function and location of the GHSR gene make it an excellent candidate gene, we tested the relation between common single nucleotide polymorphisms (SNPs) in the GHSR gene and human obesity. We performed a comprehensive analysis of SNPs, linkage disequilibrium (LD), and haplotype structure across the entire GHSR gene region (99.3 kb) in 178 pedigrees with multiple obese members (DNA of 1,095 Caucasians) and in an independent sample of the general population (MONICA Augsburg left ventricular hypertrophy substudy; DNA of 1,418 Caucasians). The LD analysis revealed a disequilibrium block consisting of five SNPs, consistent in both study cohorts. We found linkage among all five SNPs, their haplotypes, and BMI. Further, we found suggestive evidence for transmission disequilibrium for the minor SNP alleles (P < 0.05) and the two most common haplotypes with the obesity affection status ("susceptible" P = 0.025, "nonsusceptible" P = 0.045) in the family cohort using the family-based association test program. Replication of these findings in the general population resulted in stronger evidence for an association of the SNPs (best P = 0.00001) and haplotypes with the disease ("susceptible" P = 0.002, "nonsusceptible" P = 0.002). To our knowledge, these data are the first to demonstrate linkage and association of SNPs and haplotypes within the GHSR gene region and human obesity. This linkage, together with significant transmission disequilibrium in families and replication of this association in an independent population, provides evidence that common SNPs and haplotypes within the GHSR region are involved in the pathogenesis of human obesity.

Dataset Information

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas.

Publications

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas.

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