Growth hormone receptor expression in human primary gastric adenocarcinoma

The aim of this study was to determine the expression of growth hormone receptor（GHR） in patients with pri-mary gastric adenocarcinoma.We investigated 48 specimens of primary gastric adenocarcinoma and their cor-responding normal gastric mucosa.Immunohistochemistry and reverse transcription-polymerase chain reaction（RT-PCR） were used to detect the expression of GHR.Immunohistochemical analyses revealed that GHR was expressed in human primary gastric adenocarcinoma（36/48,75.0%） and appeared to be upregulated,compared to the normal mucosa（28/48,58.3%,P 〈 0.001）.A significant correlation was found between GHR expression and tumor stage（P 〈 0.001） and tumor differentiation（P 〈 0.001）.The average positive rate of ki-67 in GHR-positive tumors was 16.06%,while the positive rate in GHR-negative tumors was 6.17%（P 〈 0.01）.The average apoptosis index（AI） of GHR-positive tumors was 3.36%,which was significantly lower than that（7.33%） of GHR-negative tumors.In addition,27 of 48 cases of tumors had GHR mRNA expression,while only 17 of all 48 cases of normal mucosa did so.Our results indicate that the frequency of GHR was significantly higher in primary gastric adeno-carcinoma than that in normal gastric mucosa.GHR expression was significantly correlated with tumor differen-tiation and tumor grade.This finding supported a possible role of growth hormone in primary gastric adenocarci-noma pathophysiology.

Effect of recombinant growth hormone on expression of growth hormone receptor, insulin-like growth factor mRNA and serum level of leptin in growing pigs

Sixteen Large White ?Landrace castrated male pigs were allotted into treatment and control group. The treatment group was injected intramuscularly with recombinant porcine growth hormone (rpGH, 4 mg·d-1) and the control group with vehicle for 28 days. Animals were slaugh-tered 4 h after final injection for liver, longissimus dorsi (LD) muscle and blood sampling. Serum concentration of insulin-like growth factor 1 (IGF-I) and leptin were determined by RIA. The total RNA was extracted from tissues to measure the abundance of growth hormone receptor (GHR), IGF-I mRNA by RT-PCR with 18S rRNA internal standard. Results showed that rpGH enhanced the average daily weight gain by 26.1% (P < 0.05), the serum IGF-I concentration by 70.94% (P < 0.01), decreased serum leptin by 34.8% (P < 0.01). The relative abundance of GHR and IGFmRNA in liver were increased by 24.45% (P < 0.05) and 45.30% (P < 0.01), respectively, but no difference of GHR (P > 0.05) and IGF-I mRNA (P > 0.05) in LD between GH treated and control group was found. These results suggest that rpGH can up-regulate hepatic GHR and IGF-I gene expression and improve animal growth. However the effect of rpGH on GHR and IGF-I gene ex-pression are tissue-specific.

Cloning and Sequence Analysis on cDNA of Growth Hormone Releasing Hormone Receptor Gene from Wuzhishan Miniature Pig

[Objective] cDNA of growth hormone releasing hormone （GHRH） receptor gene from Wuzhishan miniature pig was cloned and its sequence was also analyzed. [Method] Using genomic DNA extracted from porcine ear tissues of Wuzhishan miniature pig as the template, three pairs of primers were designed by the reported cDNA sequence of porcine GHRH, and cDNA was also amplified by RT-PCR. After being recovered and purified, PCR products were ligated to pMD18-T and then transformed into Escherichia coli DH5a. The transformation products were analyzed by PCR and double enzyme digestion to screen positive clones, and the positive clones were sequenced after identification in LB liquid medium. [ Result] cDNA of Wuzhishan miniature pig GHRH receptor gene was obtained successfully, and its length was 1 577 bp coding 423 amino acids. BLAST analysis showed that there were only 23 nuoleotides in difference between this fragment and pomine GHRH receptor gene, and its homology was 98%. However, both GHRH receptor genes were constituted by 423 amino acids with the sequence homology of 96%. [ Conclusion] This study provides theoretical basis for further studies on the dwarf mechanism of Wuzhishan miniature pig.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.

Study on the Developmental Changes of Muscular GHR mRNA Expression in Sheep

[ Objective] The study aimed to explore the expression of muscular growth hormone receptor gene （GHR） in sheep at the early stage of growth and development. [Method] The GHR mRNA expression levels in longissimus dorsal muscles of male Kazak sheep and Xinjiang fine wool sheep with different ages were quantitatively analyzed by real time PCR. [ Result] Sheep GHR mRNA expression level in longissimus dorsal muscle increased firstly followed by decline, and then kept steady until the end of the experiment, with the expression peak appearing on postnatal day 30. The GHR mRNA expression level of Kazak sheep was extremely lower than that of Xingjiang fine wool sheep from 2 to 90 days old （ P 〈0.01 ）. E Conclusionl Both age and breed had great effects on the expression of muscular GHR gene in sheep.

Analysis on Polymorphisms of GHR Gene in Improved Hybrid Yellow Cattle Groups from Liupan Mountain Area in Ningxia

[Objective] The paper aimed to analyze the polymorphism of the growth hormone receptor （GHR） in improved hybrid yellow cattle group from Liupan Mountain area in Ningxia Autonomous Region,so as to provide technological basis for hybrid improvement. [Method] Polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLP） technology was carried out to examine polymorphisms of GHR gene of 70 individuals. [Result] The target fragment of 338 bp was amplified. The PCR product digested by restriction enzyme Alu I showed polymorphisms. The frequencies of the two genotypes （AA,BB） were 75.71% （53 individuals） and 24.29% （17 individuals）,respectively. [Conclusion] Two genotypes of GHR gene were detected in improved hybrid yellow cattle groups from Liupan Mountain area in Ningxia.

Developmental Changes of GHRmRNA Expression Level in Sheep Liver

[Objective] To detect the expression of liver growth hormone receptor gene （GHR） during the eady development of Kazak sheep and Xinjiang fine-wool sheep, and thus provide information for the research about the early growth and development of sheep. [ Method] With real-time quantitative PCR, the liver GHR mRNA level was separately detected in two varieties of sheep at 2, 30, 60, 90 and 120 days old. Then the data was analyzed with SPSS software. E Result] The liver GHR gene was highly expressed in 2 day-old sheep, but the expression level fell to the lowest point at 30 days old and then rose continuously; the change trend after 30 days old was positively correlated with the cumulative growth curves of sheep （ P 〈0.05） ; GHR mRNA level was lower in Kazak sheep than in Xinjiang fine-wool sheep during 2 -90 days old, but the difference was ex- tremely significant （P 〈0.01 ） only at 2 days old and 90 days old. [ Conclusion] The male Kazak sheep and Xinjiang fine-wool sheep have similar model of developmental changes of liver GHR mRNA and the differences are smaller between these two species; GHR gene may play an important role in the regulation of sheep growth.

The effects of growth hormone on therapy resistance in cancer

Pituitary derived and peripherally produced growth hormone(GH)is a crucial mediator of longitudinal growth,organ development,metabolic regulation with tissue specific,sex specific,and age-dependent effects.GH and its cognate receptor(GHR)are expressed in several forms of cancer and have been validated as an anti-cancer target through a large body of in vitro,in vivo and epidemiological analyses.However,the underlying molecular mechanisms of GH action in cancer prognosis and therapeutic response had been sparse until recently.This review assimilates the critical details of GH-GHR mediated therapy resistance across different cancer types,distilling the therapeutic implications based on our current understanding of these effects.

Sequencing and Analysis of G HR Gene from Genomic DNA Pools of Mink

In order to study the single nucleotide polymorphisms （SNPs） of growth hormone receptor （GHR） gene in mink populations, genomic DNA pools of Minghua black minks and silver-blue minks were constructed, and the 10^th exon of GHR gene was PCR amplified from the two DNA pools and sequenced. The results showed that two SNPs were found at position 209 （T/C） and position 533 （C/A） of the 10^th exon of GHR gene in the two mink populations.

Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro

Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 （GHRP-6）, increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders. Methods A diabetic guinea pig model was produced by intraperitoneal （i.p.） injection of streptozotocin （STZ, 280 mg/kg）. Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 （10-100 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor （GHS-R） antagonist, D-Lys^3-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 （100 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction （RT-PCR）. Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/kg） accelerated gastric emptying in diabetic guinea pigs with gastroparesis （n=6, P 〈0.05）. In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying （n=6, P 〈0.05）. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist （n=6, P 〈0.05）. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs （n=6, P〈0.05）. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

The cardiovascular action of hexarelin

Hexarelin, a synthetic growth hormone-releasing peptide, can bind to and activate the growth hormone secretagogue receptor （GHSR） in the brain similar to its natural analog ghrelin. However, the peripheral distribution of GHSR in the heart and blood vessels suggests that hexarelin might have direct cardiovascular actions beyond growth hormone release and neuroendocrine effects. Furthermore, the non-GHSR CD36 had been demonstrated to be a specific cardiac receptor for hexarelin and to mediate its cardioprotective effects. When compared with ghrelin, hexarelin is chemically more stable and functionally more potent. Therefore, it may be a promising therapeutic agent for some car-diovascular conditions. In this concise review, we discuss the current evidence for the cardiovascular action of hexarelin.