Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. Phorbel ester, 1,2 tetradecanoylphorbol 13 acetate (TPA) c...Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. Phorbel ester, 1,2 tetradecanoylphorbol 13 acetate (TPA) can also stimulate releasing of GH. The precise intracellular mechanism has not been entirely deciphered. We used cell cultures of human pituitary somatotrophinomas to investigate the relation between GHRP-6 and TPA on membrane phosphatidylinositol (PI) turnover and GH secretion. The results showed that the working mechanisms of GHRP-6 and TPA are not identical, although they all can stimulate GH secretion in human pituitary somatotrophinomas. This indicates that PI-PKC signal transduction system may play a crucial role in the regulation of GH secretion.展开更多
AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic mouse model was established by intraperitoneal injection w...AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated. RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT. CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.展开更多
Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encod...Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encoding the GHRH gene to pregnant mice and pig augmented long-term growth in first generation progeny,and that the administration of GHRP-6 results in growth augmentation in mice and rabbits. However,it has not yet been reported if GHRP-6 induces intergenerational growth effects in pigs. Ploy lactic-co-glycolic acid （PLGA） microsphere adsorption of treatment proteins enhances gene expression,genetic immunization and the ability to protect plasmid DNA and peptides from degradation. The cur-rent study was conducted to determine the growth performance of piglets born to gilts treated with GHRP-6 incorporated into thermosensitive PLGA-PEG-PLGA triblock copolymers. Gilts were injected intra-muscularly once at day 85 of gestation with 30 mg of GHRP6-loaded thermosensitive PLGA-PEG-PLGA triblock copolymers. Piglets were weighed periodically between birth and 28 days. Mean body weights of piglets born to GHRP-6-treated gilts were 6. 58% to 18. 89% （P 〈 0. 05 ） greater than those of piglets born to control gilts. This study confirms that enhanced maternal GHRP-6 mediated by thermosensitive PLGA-PEG-PLGA can augment growth of piglets.展开更多
In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) r...In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC) dependent GH releasing peptide (GHRP 6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP 6 exerted significant stimulatory effect on cAMP production by 2 gsp positive tumors and no effect on the gsp negative tumors. GHRP 6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP 6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross talk between the two intracellular signal transduction pathways in pituitary cells.展开更多
文摘Growth hormone releasing peptide (GHRP-6) is a synthetic hexapeptide which specifically stimulates secretion of growth hormone (GH) by pituitary somatotrophs. Phorbel ester, 1,2 tetradecanoylphorbol 13 acetate (TPA) can also stimulate releasing of GH. The precise intracellular mechanism has not been entirely deciphered. We used cell cultures of human pituitary somatotrophinomas to investigate the relation between GHRP-6 and TPA on membrane phosphatidylinositol (PI) turnover and GH secretion. The results showed that the working mechanisms of GHRP-6 and TPA are not identical, although they all can stimulate GH secretion in human pituitary somatotrophinomas. This indicates that PI-PKC signal transduction system may play a crucial role in the regulation of GH secretion.
基金National Natural Science Foundation of China, No. 30400429
文摘AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice. METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated. RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT. CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
基金supported by grants from the National Natural Science Foundation of China (u0731004, 30771572 )the National Basic Research Program of China (2009CB941601)the Hebei Province Nature Science Foundation (0722553)
文摘Both growth hormone-releasing peptide 6 （GHRP-6） and growth hormone-releasing hormone （GHRH） have potent GH-releasing activity in animals. We have previously demonstrated that the administration of a plasmid encoding the GHRH gene to pregnant mice and pig augmented long-term growth in first generation progeny,and that the administration of GHRP-6 results in growth augmentation in mice and rabbits. However,it has not yet been reported if GHRP-6 induces intergenerational growth effects in pigs. Ploy lactic-co-glycolic acid （PLGA） microsphere adsorption of treatment proteins enhances gene expression,genetic immunization and the ability to protect plasmid DNA and peptides from degradation. The cur-rent study was conducted to determine the growth performance of piglets born to gilts treated with GHRP-6 incorporated into thermosensitive PLGA-PEG-PLGA triblock copolymers. Gilts were injected intra-muscularly once at day 85 of gestation with 30 mg of GHRP6-loaded thermosensitive PLGA-PEG-PLGA triblock copolymers. Piglets were weighed periodically between birth and 28 days. Mean body weights of piglets born to GHRP-6-treated gilts were 6. 58% to 18. 89% （P 〈 0. 05 ） greater than those of piglets born to control gilts. This study confirms that enhanced maternal GHRP-6 mediated by thermosensitive PLGA-PEG-PLGA can augment growth of piglets.
基金This project was supported by the grants from National Natural Science Foundation of China (No. 396 70 736 ) Deutsche Gesel
文摘In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA) dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC) dependent GH releasing peptide (GHRP 6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP 6 exerted significant stimulatory effect on cAMP production by 2 gsp positive tumors and no effect on the gsp negative tumors. GHRP 6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP 6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross talk between the two intracellular signal transduction pathways in pituitary cells.
