Oral arginine improves linear growth of long bones and the neuroendocrine mechanism

Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)...

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Veröffentlicht in:Neuroscience bulletin 2011-06, Vol.27 (3), p.156-162
Hauptverfasser: Jiang, Ming-Yu, Cai, De-Pei
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description Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L -arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase ( nNOS ), soluble guanylyl cyclases ( sGCα1 and sGCβ1 ), growth hormone-releasing hormone ( Ghrh ) and somatostatin ( SS ) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased ( P < 0.05), and serum GH concentration was elevated ( P < 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 ( P < 0.05), as well as the expression of Gh mRNA ( P < 0.01), were significantly up-regulated, while the expression of SS mRNA was downregulated ( P < 0.05). Conclusion Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.
doi_str_mv 10.1007/s12264-011-1051-3
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Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L -arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase ( nNOS ), soluble guanylyl cyclases ( sGCα1 and sGCβ1 ), growth hormone-releasing hormone ( Ghrh ) and somatostatin ( SS ) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased ( P &lt; 0.05), and serum GH concentration was elevated ( P &lt; 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 ( P &lt; 0.05), as well as the expression of Gh mRNA ( P &lt; 0.01), were significantly up-regulated, while the expression of SS mRNA was downregulated ( P &lt; 0.05). Conclusion Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.</description><identifier>ISSN: 1673-7067</identifier><identifier>EISSN: 1995-8218</identifier><identifier>DOI: 10.1007/s12264-011-1051-3</identifier><identifier>PMID: 21614098</identifier><language>eng</language><publisher>Heidelberg: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences</publisher><subject>Anatomy ; Anesthesiology ; Animals ; Arginine - administration &amp; dosage ; Arginine - physiology ; Biomedical and Life Sciences ; Biomedicine ; Bone Development - drug effects ; Bone Development - physiology ; Cyclic GMP - metabolism ; Femur - drug effects ; Femur - physiology ; Growth Hormone - blood ; Growth Hormone - drug effects ; Growth Plate - drug effects ; Growth Plate - metabolism ; Guanylate Cyclase - drug effects ; Guanylate Cyclase - genetics ; Guanylate Cyclase - metabolism ; Human Physiology ; Hypothalamo-Hypophyseal System - drug effects ; Hypothalamo-Hypophyseal System - physiology ; Male ; Neurology ; Neurosciences ; Nitric Oxide Synthase Type I - drug effects ; Nitric Oxide Synthase Type I - genetics ; Nitric Oxide Synthase Type I - metabolism ; Original ; Original Article ; Pain Medicine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear - drug effects ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; RNA, Messenger - analysis ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Soluble Guanylyl Cyclase ; Tibia - drug effects ; Tibia - physiology</subject><ispartof>Neuroscience bulletin, 2011-06, Vol.27 (3), p.156-162</ispartof><rights>Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-3dc71579c827b314fca16e923ad3d44afb9b2e51a6d442b9a80e1e25fa784c6f3</citedby><cites>FETCH-LOGICAL-c441t-3dc71579c827b314fca16e923ad3d44afb9b2e51a6d442b9a80e1e25fa784c6f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560364/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560364/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21614098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Ming-Yu</creatorcontrib><creatorcontrib>Cai, De-Pei</creatorcontrib><title>Oral arginine improves linear growth of long bones and the neuroendocrine mechanism</title><title>Neuroscience bulletin</title><addtitle>Neurosci. Bull</addtitle><addtitle>Neurosci Bull</addtitle><description>Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L -arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase ( nNOS ), soluble guanylyl cyclases ( sGCα1 and sGCβ1 ), growth hormone-releasing hormone ( Ghrh ) and somatostatin ( SS ) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased ( P &lt; 0.05), and serum GH concentration was elevated ( P &lt; 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 ( P &lt; 0.05), as well as the expression of Gh mRNA ( P &lt; 0.01), were significantly up-regulated, while the expression of SS mRNA was downregulated ( P &lt; 0.05). Conclusion Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.</description><subject>Anatomy</subject><subject>Anesthesiology</subject><subject>Animals</subject><subject>Arginine - administration &amp; dosage</subject><subject>Arginine - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone Development - drug effects</subject><subject>Bone Development - physiology</subject><subject>Cyclic GMP - metabolism</subject><subject>Femur - drug effects</subject><subject>Femur - physiology</subject><subject>Growth Hormone - blood</subject><subject>Growth Hormone - drug effects</subject><subject>Growth Plate - drug effects</subject><subject>Growth Plate - metabolism</subject><subject>Guanylate Cyclase - drug effects</subject><subject>Guanylate Cyclase - genetics</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Human Physiology</subject><subject>Hypothalamo-Hypophyseal System - drug effects</subject><subject>Hypothalamo-Hypophyseal System - physiology</subject><subject>Male</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Nitric Oxide Synthase Type I - drug effects</subject><subject>Nitric Oxide Synthase Type I - genetics</subject><subject>Nitric Oxide Synthase Type I - metabolism</subject><subject>Original</subject><subject>Original Article</subject><subject>Pain Medicine</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Cytoplasmic and Nuclear - drug effects</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Soluble Guanylyl Cyclase</subject><subject>Tibia - drug effects</subject><subject>Tibia - physiology</subject><issn>1673-7067</issn><issn>1995-8218</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1TAQtRAVfcAHsEHesQp4bMePDRKqaEGq1EVhbTnOJDdVYl_spBV_j69uqWDDamZ0HmPPIeQtsA_AmP5YgHMlGwbQAGuhES_IGVjbNoaDeVl7pUWjmdKn5LyUe8YU00K-IqccFEhmzRm5u81-pj6PU5wi0mnZ5_SAhc518pmOOT2uO5oGOqc40i7FivnY03WHNOKWE8Y-hXzQLhh2Pk5leU1OBj8XfPNUL8iPqy_fL782N7fX3y4_3zRBSlgb0QcNrbbBcN0JkEPwoNBy4XvRS-mHznYcW_CqTryz3jAE5O3gtZFBDeKCfDr67rduwT5gXOtn3D5Pi8-_XPKT-xeJ086N6cG1rWJCyWrw_skgp58bltUtUwk4zz5i2oozylhrFPDKhCMz5FRKxuF5CzB3yMIds3A1C3fIwomqeff3854Vf45fCfxIKBWKI2Z3n7Yc68n-4_obrq2WtQ</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Jiang, Ming-Yu</creator><creator>Cai, De-Pei</creator><general>Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110601</creationdate><title>Oral arginine improves linear growth of long bones and the neuroendocrine mechanism</title><author>Jiang, Ming-Yu ; Cai, De-Pei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-3dc71579c827b314fca16e923ad3d44afb9b2e51a6d442b9a80e1e25fa784c6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anatomy</topic><topic>Anesthesiology</topic><topic>Animals</topic><topic>Arginine - administration &amp; dosage</topic><topic>Arginine - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone Development - drug effects</topic><topic>Bone Development - physiology</topic><topic>Cyclic GMP - metabolism</topic><topic>Femur - drug effects</topic><topic>Femur - physiology</topic><topic>Growth Hormone - blood</topic><topic>Growth Hormone - drug effects</topic><topic>Growth Plate - drug effects</topic><topic>Growth Plate - metabolism</topic><topic>Guanylate Cyclase - drug effects</topic><topic>Guanylate Cyclase - genetics</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Human Physiology</topic><topic>Hypothalamo-Hypophyseal System - drug effects</topic><topic>Hypothalamo-Hypophyseal System - physiology</topic><topic>Male</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Nitric Oxide Synthase Type I - drug effects</topic><topic>Nitric Oxide Synthase Type I - genetics</topic><topic>Nitric Oxide Synthase Type I - metabolism</topic><topic>Original</topic><topic>Original Article</topic><topic>Pain Medicine</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Cytoplasmic and Nuclear - drug effects</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>RNA, Messenger - analysis</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Soluble Guanylyl Cyclase</topic><topic>Tibia - drug effects</topic><topic>Tibia - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Ming-Yu</creatorcontrib><creatorcontrib>Cai, De-Pei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuroscience bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Ming-Yu</au><au>Cai, De-Pei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral arginine improves linear growth of long bones and the neuroendocrine mechanism</atitle><jtitle>Neuroscience bulletin</jtitle><stitle>Neurosci. Bull</stitle><addtitle>Neurosci Bull</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>27</volume><issue>3</issue><spage>156</spage><epage>162</epage><pages>156-162</pages><issn>1673-7067</issn><eissn>1995-8218</eissn><abstract>Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L -arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase ( nNOS ), soluble guanylyl cyclases ( sGCα1 and sGCβ1 ), growth hormone-releasing hormone ( Ghrh ) and somatostatin ( SS ) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased ( P &lt; 0.05), and serum GH concentration was elevated ( P &lt; 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 ( P &lt; 0.05), as well as the expression of Gh mRNA ( P &lt; 0.01), were significantly up-regulated, while the expression of SS mRNA was downregulated ( P &lt; 0.05). Conclusion Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.</abstract><cop>Heidelberg</cop><pub>Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences</pub><pmid>21614098</pmid><doi>10.1007/s12264-011-1051-3</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings
subjects Anatomy
Anesthesiology
Animals
Arginine - administration & dosage
Arginine - physiology
Biomedical and Life Sciences
Biomedicine
Bone Development - drug effects
Bone Development - physiology
Cyclic GMP - metabolism
Femur - drug effects
Femur - physiology
Growth Hormone - blood
Growth Hormone - drug effects
Growth Plate - drug effects
Growth Plate - metabolism
Guanylate Cyclase - drug effects
Guanylate Cyclase - genetics
Guanylate Cyclase - metabolism
Human Physiology
Hypothalamo-Hypophyseal System - drug effects
Hypothalamo-Hypophyseal System - physiology
Male
Neurology
Neurosciences
Nitric Oxide Synthase Type I - drug effects
Nitric Oxide Synthase Type I - genetics
Nitric Oxide Synthase Type I - metabolism
Original
Original Article
Pain Medicine
Random Allocation
Rats
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear - drug effects
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
RNA, Messenger - analysis
Signal Transduction - drug effects
Signal Transduction - physiology
Soluble Guanylyl Cyclase
Tibia - drug effects
Tibia - physiology
title Oral arginine improves linear growth of long bones and the neuroendocrine mechanism
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