The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy
Summary Objective Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH rec...
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| Veröffentlicht in: | Clinical endocrinology (Oxford) 2010-06, Vol.72 (6), p.800-806 |
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| creator | Fernández-Pérez, L. Nóvoa, J. Ståhlberg, N. Santana-Farré, R. Boronat, M. Marrero, D. Henríquez-Hernández, L. Norstedt, G. Flores-Morales, A. |
| description | Summary
Objective Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH receptors are expressed in certain blood cell types, changes in gene expression in peripheral blood can reflect perturbations induced as a result of GH therapy.
Design/patients We have carried out a pilot study to identify GH‐responsive genes in blood, and have assessed the utility of GH‐responsive genes in monitoring GH therapy in AGHD. Blood was collected from ten women diagnosed with AGHD syndrome both before and 4 weeks after initiation of GH substitutive therapy. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and changes in response to GH were detected using microarray‐based gene analysis.
Results All patients responded to GH replacement therapy, with serum levels of IGF‐I increasing by an average of 307% (P = 0·0003) while IGFBP‐3 increased by an average of 182% (P = 0·0002). Serum levels of triglycerides, LDL‐C, HDL‐C, APOA1 or APOB did not change after 1 month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels (P = 0·0149). Using a stringent selection cutoff of P ≤ 0·05, paired analysis identified a set of transcripts that correlated with GH administration. We applied the multivariate statistical technique PLS‐DA to the changes in gene expression, demonstrating their utility in differentiating untreated patients and those undergoing GH replacement therapy.
Conclusion This study shows that GH‐dependent effects on gene expression in PBMCs can be detected by microarray‐based gene analysis, and our results establish a foundation for the further exploration of peripheral blood as a surrogate to detect exposure to GH therapy. |
| doi_str_mv | 10.1111/j.1365-2265.2009.03732.x |
| format | Article |
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Objective Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH receptors are expressed in certain blood cell types, changes in gene expression in peripheral blood can reflect perturbations induced as a result of GH therapy.
Design/patients We have carried out a pilot study to identify GH‐responsive genes in blood, and have assessed the utility of GH‐responsive genes in monitoring GH therapy in AGHD. Blood was collected from ten women diagnosed with AGHD syndrome both before and 4 weeks after initiation of GH substitutive therapy. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and changes in response to GH were detected using microarray‐based gene analysis.
Results All patients responded to GH replacement therapy, with serum levels of IGF‐I increasing by an average of 307% (P = 0·0003) while IGFBP‐3 increased by an average of 182% (P = 0·0002). Serum levels of triglycerides, LDL‐C, HDL‐C, APOA1 or APOB did not change after 1 month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels (P = 0·0149). Using a stringent selection cutoff of P ≤ 0·05, paired analysis identified a set of transcripts that correlated with GH administration. We applied the multivariate statistical technique PLS‐DA to the changes in gene expression, demonstrating their utility in differentiating untreated patients and those undergoing GH replacement therapy.
Conclusion This study shows that GH‐dependent effects on gene expression in PBMCs can be detected by microarray‐based gene analysis, and our results establish a foundation for the further exploration of peripheral blood as a surrogate to detect exposure to GH therapy.</description><identifier>ISSN: 0300-0664</identifier><identifier>ISSN: 1365-2265</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1111/j.1365-2265.2009.03732.x</identifier><identifier>PMID: 19849699</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Biological and medical sciences ; Biomarkers, Pharmacological - blood ; Biomarkers, Pharmacological - metabolism ; Blood ; Blood Proteins - genetics ; Diagnostic Techniques, Endocrine ; Endocrinopathies ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression - drug effects ; Gene Expression Profiling ; Growth Disorders - blood ; Growth Disorders - diagnosis ; Growth Disorders - drug therapy ; Growth Disorders - genetics ; Growth hormones ; Hormone Replacement Therapy ; Human Growth Hormone - deficiency ; Human Growth Hormone - pharmacology ; Human Growth Hormone - therapeutic use ; Humans ; Hypopituitarism - blood ; Hypopituitarism - drug therapy ; Hypopituitarism - genetics ; Medical sciences ; Medicin och hälsovetenskap ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pediatrics ; Prognosis ; Vertebrates: endocrinology ; Young Adult</subject><ispartof>Clinical endocrinology (Oxford), 2010-06, Vol.72 (6), p.800-806</ispartof><rights>2010 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5522-e1fc220a8d3efb50ec3503074b8a50cb5840a588f487eb8e8e81cd716e152b063</citedby><cites>FETCH-LOGICAL-c5522-e1fc220a8d3efb50ec3503074b8a50cb5840a588f487eb8e8e81cd716e152b063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2265.2009.03732.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2265.2009.03732.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22758782$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19849699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:120453117$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernández-Pérez, L.</creatorcontrib><creatorcontrib>Nóvoa, J.</creatorcontrib><creatorcontrib>Ståhlberg, N.</creatorcontrib><creatorcontrib>Santana-Farré, R.</creatorcontrib><creatorcontrib>Boronat, M.</creatorcontrib><creatorcontrib>Marrero, D.</creatorcontrib><creatorcontrib>Henríquez-Hernández, L.</creatorcontrib><creatorcontrib>Norstedt, G.</creatorcontrib><creatorcontrib>Flores-Morales, A.</creatorcontrib><title>The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description>Summary
Objective Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH receptors are expressed in certain blood cell types, changes in gene expression in peripheral blood can reflect perturbations induced as a result of GH therapy.
Design/patients We have carried out a pilot study to identify GH‐responsive genes in blood, and have assessed the utility of GH‐responsive genes in monitoring GH therapy in AGHD. Blood was collected from ten women diagnosed with AGHD syndrome both before and 4 weeks after initiation of GH substitutive therapy. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and changes in response to GH were detected using microarray‐based gene analysis.
Results All patients responded to GH replacement therapy, with serum levels of IGF‐I increasing by an average of 307% (P = 0·0003) while IGFBP‐3 increased by an average of 182% (P = 0·0002). Serum levels of triglycerides, LDL‐C, HDL‐C, APOA1 or APOB did not change after 1 month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels (P = 0·0149). Using a stringent selection cutoff of P ≤ 0·05, paired analysis identified a set of transcripts that correlated with GH administration. We applied the multivariate statistical technique PLS‐DA to the changes in gene expression, demonstrating their utility in differentiating untreated patients and those undergoing GH replacement therapy.
Conclusion This study shows that GH‐dependent effects on gene expression in PBMCs can be detected by microarray‐based gene analysis, and our results establish a foundation for the further exploration of peripheral blood as a surrogate to detect exposure to GH therapy.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Pharmacological - blood</subject><subject>Biomarkers, Pharmacological - metabolism</subject><subject>Blood</subject><subject>Blood Proteins - genetics</subject><subject>Diagnostic Techniques, Endocrine</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Profiling</subject><subject>Growth Disorders - blood</subject><subject>Growth Disorders - diagnosis</subject><subject>Growth Disorders - drug therapy</subject><subject>Growth Disorders - genetics</subject><subject>Growth hormones</subject><subject>Hormone Replacement Therapy</subject><subject>Human Growth Hormone - deficiency</subject><subject>Human Growth Hormone - pharmacology</subject><subject>Human Growth Hormone - therapeutic use</subject><subject>Humans</subject><subject>Hypopituitarism - blood</subject><subject>Hypopituitarism - drug therapy</subject><subject>Hypopituitarism - genetics</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pediatrics</subject><subject>Prognosis</subject><subject>Vertebrates: endocrinology</subject><subject>Young Adult</subject><issn>0300-0664</issn><issn>1365-2265</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks2O0zAUhSMEYsrAKyBLCLFK8U8cOwsWqBoG0DAgKGJpOc7N1J00zthJf56KV8ShpZUGIREvYl1_5_r46iQJInhK4vd6OSUs5ymlOZ9SjIspZoLR6fZBMjkePEwmmGGc4jzPzpInISwxxlxi8Tg5I4XMirwoJsnP-QIQ1DWYHrka2Rat7dqhG-82_QItnF-5FlDvQfcraCPTorJxrkI3EOuw7TyEYGM1KnU1NH1AGxuV9xpUUFtjoTU75GENugmoc31saHWDSutW2t-CD6h3KPK2d_4vCwvwuts9TR7VUQ3PDv_z5Pu7i_nsfXr1-fLD7O1VajinNAVSG0qxlhWDuuQYDONxGiIrpebYlFxmWHMp60wKKCXERUwlSA6E0xLn7DxJ933DBrqhVJ230eNOOW3VoXQbd6B4vA_zyBf_5DvvqpPoj5BQnHFGiIjaV3ttBO8GCL1a2WCgaXQLbghKMJYJzooski_ukUs3-DYOQhGexfdkgoxe5J4y3oXgoT66IViN-VFLNcZEjTFRY37U7_yobZQ-P1wwlCuoTsJDYCLw8gDoYHRTe90aG44cpYJLIWnk3uy5jW1g998G1Ozietyd5m9DD9ujPsZE5YIJrn5cX6ov-Cuff_xG1Sf2C1Jk9VU</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Fernández-Pérez, L.</creator><creator>Nóvoa, J.</creator><creator>Ståhlberg, N.</creator><creator>Santana-Farré, R.</creator><creator>Boronat, M.</creator><creator>Marrero, D.</creator><creator>Henríquez-Hernández, L.</creator><creator>Norstedt, G.</creator><creator>Flores-Morales, A.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>201006</creationdate><title>The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy</title><author>Fernández-Pérez, L. ; Nóvoa, J. ; Ståhlberg, N. ; Santana-Farré, R. ; Boronat, M. ; Marrero, D. ; Henríquez-Hernández, L. ; Norstedt, G. ; Flores-Morales, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5522-e1fc220a8d3efb50ec3503074b8a50cb5840a588f487eb8e8e81cd716e152b063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Pharmacological - blood</topic><topic>Biomarkers, Pharmacological - metabolism</topic><topic>Blood</topic><topic>Blood Proteins - genetics</topic><topic>Diagnostic Techniques, Endocrine</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression Profiling</topic><topic>Growth Disorders - blood</topic><topic>Growth Disorders - diagnosis</topic><topic>Growth Disorders - drug therapy</topic><topic>Growth Disorders - genetics</topic><topic>Growth hormones</topic><topic>Hormone Replacement Therapy</topic><topic>Human Growth Hormone - deficiency</topic><topic>Human Growth Hormone - pharmacology</topic><topic>Human Growth Hormone - therapeutic use</topic><topic>Humans</topic><topic>Hypopituitarism - blood</topic><topic>Hypopituitarism - drug therapy</topic><topic>Hypopituitarism - genetics</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pediatrics</topic><topic>Prognosis</topic><topic>Vertebrates: endocrinology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernández-Pérez, L.</creatorcontrib><creatorcontrib>Nóvoa, J.</creatorcontrib><creatorcontrib>Ståhlberg, N.</creatorcontrib><creatorcontrib>Santana-Farré, R.</creatorcontrib><creatorcontrib>Boronat, M.</creatorcontrib><creatorcontrib>Marrero, D.</creatorcontrib><creatorcontrib>Henríquez-Hernández, L.</creatorcontrib><creatorcontrib>Norstedt, G.</creatorcontrib><creatorcontrib>Flores-Morales, A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernández-Pérez, L.</au><au>Nóvoa, J.</au><au>Ståhlberg, N.</au><au>Santana-Farré, R.</au><au>Boronat, M.</au><au>Marrero, D.</au><au>Henríquez-Hernández, L.</au><au>Norstedt, G.</au><au>Flores-Morales, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2010-06</date><risdate>2010</risdate><volume>72</volume><issue>6</issue><spage>800</spage><epage>806</epage><pages>800-806</pages><issn>0300-0664</issn><issn>1365-2265</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>Summary
Objective Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH receptors are expressed in certain blood cell types, changes in gene expression in peripheral blood can reflect perturbations induced as a result of GH therapy.
Design/patients We have carried out a pilot study to identify GH‐responsive genes in blood, and have assessed the utility of GH‐responsive genes in monitoring GH therapy in AGHD. Blood was collected from ten women diagnosed with AGHD syndrome both before and 4 weeks after initiation of GH substitutive therapy. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and changes in response to GH were detected using microarray‐based gene analysis.
Results All patients responded to GH replacement therapy, with serum levels of IGF‐I increasing by an average of 307% (P = 0·0003) while IGFBP‐3 increased by an average of 182% (P = 0·0002). Serum levels of triglycerides, LDL‐C, HDL‐C, APOA1 or APOB did not change after 1 month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels (P = 0·0149). Using a stringent selection cutoff of P ≤ 0·05, paired analysis identified a set of transcripts that correlated with GH administration. We applied the multivariate statistical technique PLS‐DA to the changes in gene expression, demonstrating their utility in differentiating untreated patients and those undergoing GH replacement therapy.
Conclusion This study shows that GH‐dependent effects on gene expression in PBMCs can be detected by microarray‐based gene analysis, and our results establish a foundation for the further exploration of peripheral blood as a surrogate to detect exposure to GH therapy.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19849699</pmid><doi>10.1111/j.1365-2265.2009.03732.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences Biomarkers, Pharmacological - blood Biomarkers, Pharmacological - metabolism Blood Blood Proteins - genetics Diagnostic Techniques, Endocrine Endocrinopathies Female Fundamental and applied biological sciences. Psychology Gene expression Gene Expression - drug effects Gene Expression Profiling Growth Disorders - blood Growth Disorders - diagnosis Growth Disorders - drug therapy Growth Disorders - genetics Growth hormones Hormone Replacement Therapy Human Growth Hormone - deficiency Human Growth Hormone - pharmacology Human Growth Hormone - therapeutic use Humans Hypopituitarism - blood Hypopituitarism - drug therapy Hypopituitarism - genetics Medical sciences Medicin och hälsovetenskap Middle Aged Oligonucleotide Array Sequence Analysis Pediatrics Prognosis Vertebrates: endocrinology Young Adult |
| title | The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy |
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