Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 - implications for steroid-induced myopathy
Summary Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects. Objective To determine if administration of the potent glucocorticoid d...
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| Veröffentlicht in: | Clinical endocrinology (Oxford) 2010-07, Vol.73 (1), p.126-132 |
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| creator | Inder, Warrick J. Jang, Christina Obeyesekere, Varuni R. Alford, Frank P. |
| description | Summary
Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects.
Objective To determine if administration of the potent glucocorticoid dexamethasone down‐regulates SkM androgen receptor and the IGF‐1 signalling pathway.
Methods and subjects Twenty‐four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days.
Main outcome measures Changes in plasma testosterone and IGF‐1, SkM androgen receptor mRNA, SkM IGF‐1mRNA and SkM IGF‐1 receptor mRNA by quantitative RT‐PCR after dexamethasone.
Results Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF‐1 and SkM expression of IGF‐1 and IGF‐1 receptor were also similar between males and females. Following dexamethasone, there was a significant down‐regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P |
| doi_str_mv | 10.1111/j.1365-2265.2009.03683.x |
| format | Article |
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Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects.
Objective To determine if administration of the potent glucocorticoid dexamethasone down‐regulates SkM androgen receptor and the IGF‐1 signalling pathway.
Methods and subjects Twenty‐four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days.
Main outcome measures Changes in plasma testosterone and IGF‐1, SkM androgen receptor mRNA, SkM IGF‐1mRNA and SkM IGF‐1 receptor mRNA by quantitative RT‐PCR after dexamethasone.
Results Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF‐1 and SkM expression of IGF‐1 and IGF‐1 receptor were also similar between males and females. Following dexamethasone, there was a significant down‐regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P < 0·05) and IGF‐1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P < 0·05) mRNA, but no change in expression of the IGF‐1 receptor. Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P < 0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P < 0·05).
Conclusions Exogenous steroid excess results in relative androgen deficiency at two levels, reduced circulating testosterone and SkM androgen receptor mRNA, along with reduced SkM IGF‐1 mRNA. These defects may contribute to the development of steroid‐induced myopathy.</description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1111/j.1365-2265.2009.03683.x</identifier><identifier>PMID: 19681914</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Dexamethasone - adverse effects ; Dexamethasone - pharmacology ; Diabetes Mellitus, Type 2 - metabolism ; Down-Regulation ; Endocrinopathies ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Insulin-Like Growth Factor I - biosynthesis ; Male ; Medical sciences ; Middle Aged ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscular Diseases - chemically induced ; Muscular Diseases - metabolism ; Receptor, IGF Type 1 - biosynthesis ; Receptors, Androgen - biosynthesis ; RNA, Messenger - metabolism ; Testosterone - blood ; Vertebrates: endocrinology</subject><ispartof>Clinical endocrinology (Oxford), 2010-07, Vol.73 (1), p.126-132</ispartof><rights>2010 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5303-ee8d30fb3fb034c6e8d82c83153d7f37be3455ae403dbb158be75c29f531770e3</citedby><cites>FETCH-LOGICAL-c5303-ee8d30fb3fb034c6e8d82c83153d7f37be3455ae403dbb158be75c29f531770e3</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.1365-2265.2009.03683.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2265.2009.03683.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22861293$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19681914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inder, Warrick J.</creatorcontrib><creatorcontrib>Jang, Christina</creatorcontrib><creatorcontrib>Obeyesekere, Varuni R.</creatorcontrib><creatorcontrib>Alford, Frank P.</creatorcontrib><title>Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 - implications for steroid-induced myopathy</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description>Summary
Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects.
Objective To determine if administration of the potent glucocorticoid dexamethasone down‐regulates SkM androgen receptor and the IGF‐1 signalling pathway.
Methods and subjects Twenty‐four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days.
Main outcome measures Changes in plasma testosterone and IGF‐1, SkM androgen receptor mRNA, SkM IGF‐1mRNA and SkM IGF‐1 receptor mRNA by quantitative RT‐PCR after dexamethasone.
Results Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF‐1 and SkM expression of IGF‐1 and IGF‐1 receptor were also similar between males and females. Following dexamethasone, there was a significant down‐regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P < 0·05) and IGF‐1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P < 0·05) mRNA, but no change in expression of the IGF‐1 receptor. Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P < 0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P < 0·05).
Conclusions Exogenous steroid excess results in relative androgen deficiency at two levels, reduced circulating testosterone and SkM androgen receptor mRNA, along with reduced SkM IGF‐1 mRNA. These defects may contribute to the development of steroid‐induced myopathy.</description><subject>Biological and medical sciences</subject><subject>Dexamethasone - adverse effects</subject><subject>Dexamethasone - pharmacology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Down-Regulation</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I - biosynthesis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscular Diseases - chemically induced</subject><subject>Muscular Diseases - metabolism</subject><subject>Receptor, IGF Type 1 - biosynthesis</subject><subject>Receptors, Androgen - biosynthesis</subject><subject>RNA, Messenger - metabolism</subject><subject>Testosterone - blood</subject><subject>Vertebrates: endocrinology</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks2O0zAURiMEYsrAKyBLCLFKsXPjxFmwgDItI42KEIOYneU4N9SdJA52ItKn4JVxplWRWOGN_865vtLnKCKMLlkYb_dLBhmPkyTjy4TSYkkhE7CcHkWL88XjaEGB0phmWXoRPfN-TynlguZPowtWZIIVLF1Evz_ipFocdsrbDomqWtMZPzg1GNsR0-1MaQZP_D02OKiGtKPXDRKceofez4ytybALZlc5-wM74lBjP1g3n5DrzTpmJCam7RujH4p6UodLP6CzpopNV40aK9IebK-G3eF59KRWjccXp_ky-ra-ul19im8-b65X729izYFCjCgqoHUJdUkh1VnYikQLYByqvIa8REg5V5hSqMqScVFiznVS1BxYnlOEy-jNsW7v7M8R_SBb4zU2jerQjl7mAEWRQsYC-eofcm9H14XmJOMpFyJNiyJQ4khpZ713WMvemVa5g2RUzpnJvZyjkXM0cs5MPmQmp6C-PD0wli1Wf8VTSAF4fQKU16qpneq08WcuSUTGkgIC9-7I_TINHv67Abm62s6r4MdHP3wAnM6-cvcyyyHn8vt2I7_efbhbb9e38gv8AV9Yw6g</recordid><startdate>201007</startdate><enddate>201007</enddate><creator>Inder, Warrick J.</creator><creator>Jang, Christina</creator><creator>Obeyesekere, Varuni R.</creator><creator>Alford, Frank P.</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></search><sort><creationdate>201007</creationdate><title>Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 - implications for steroid-induced myopathy</title><author>Inder, Warrick J. ; Jang, Christina ; Obeyesekere, Varuni R. ; Alford, Frank P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5303-ee8d30fb3fb034c6e8d82c83153d7f37be3455ae403dbb158be75c29f531770e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biological and medical sciences</topic><topic>Dexamethasone - adverse effects</topic><topic>Dexamethasone - pharmacology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Down-Regulation</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor I - biosynthesis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscular Diseases - chemically induced</topic><topic>Muscular Diseases - metabolism</topic><topic>Receptor, IGF Type 1 - biosynthesis</topic><topic>Receptors, Androgen - biosynthesis</topic><topic>RNA, Messenger - metabolism</topic><topic>Testosterone - blood</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inder, Warrick J.</creatorcontrib><creatorcontrib>Jang, Christina</creatorcontrib><creatorcontrib>Obeyesekere, Varuni R.</creatorcontrib><creatorcontrib>Alford, Frank P.</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><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inder, Warrick J.</au><au>Jang, Christina</au><au>Obeyesekere, Varuni R.</au><au>Alford, Frank P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 - implications for steroid-induced myopathy</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2010-07</date><risdate>2010</risdate><volume>73</volume><issue>1</issue><spage>126</spage><epage>132</epage><pages>126-132</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>Summary
Context Glucocorticoids are a well‐recognized cause of muscle weakness. The early effects of glucocorticoids on skeletal muscle (SkM) androgen and IGF‐1 pathways have not been previously investigated in human subjects.
Objective To determine if administration of the potent glucocorticoid dexamethasone down‐regulates SkM androgen receptor and the IGF‐1 signalling pathway.
Methods and subjects Twenty‐four subjects (12 men and 12 women), including 12 with type 2 diabetes and 12 nondiabetics were enrolled. Venous blood sampling and biopsy of vastus lateralis were performed before and after administration of oral dexamethasone 4 mg/day for 4 days.
Main outcome measures Changes in plasma testosterone and IGF‐1, SkM androgen receptor mRNA, SkM IGF‐1mRNA and SkM IGF‐1 receptor mRNA by quantitative RT‐PCR after dexamethasone.
Results Relative expression of SkM androgen receptor was similar in male (1·63 ± 0·37) vs. female (1·57 ± 0·30) subjects, despite the significant difference in plasma testosterone levels. Plasma IGF‐1 and SkM expression of IGF‐1 and IGF‐1 receptor were also similar between males and females. Following dexamethasone, there was a significant down‐regulation of SkM androgen receptor (1·60 ± 0·23 vs. 1·11 ± 0·16, P < 0·05) and IGF‐1 (1·72 ± 0·29 vs. 1·06 ± 0·14, P < 0·05) mRNA, but no change in expression of the IGF‐1 receptor. Plasma testosterone fell significantly in both sexes (male: 15·0 ± 1·3 vs. 11·3 ± 1·2 nmol/l, P < 0·01, female: 1·8 ± 0·5 vs. 0·5 ± 0·1 nmol/l, P < 0·05).
Conclusions Exogenous steroid excess results in relative androgen deficiency at two levels, reduced circulating testosterone and SkM androgen receptor mRNA, along with reduced SkM IGF‐1 mRNA. These defects may contribute to the development of steroid‐induced myopathy.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19681914</pmid><doi>10.1111/j.1365-2265.2009.03683.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Biological and medical sciences Dexamethasone - adverse effects Dexamethasone - pharmacology Diabetes Mellitus, Type 2 - metabolism Down-Regulation Endocrinopathies Female Fundamental and applied biological sciences. Psychology Humans Insulin-Like Growth Factor I - biosynthesis Male Medical sciences Middle Aged Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscular Diseases - chemically induced Muscular Diseases - metabolism Receptor, IGF Type 1 - biosynthesis Receptors, Androgen - biosynthesis RNA, Messenger - metabolism Testosterone - blood Vertebrates: endocrinology |
| title | Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1 - implications for steroid-induced myopathy |
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