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Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit
Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined. The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during...
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| Published in: | The journal of clinical endocrinology and metabolism 2022-08, Vol.107 (8), p.e3254-e3263 |
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| creator | Howard, Emily E Shankaran, Mahalakshmi Evans, Willian J Berryman, Claire E Margolis, Lee M Lieberman, Harris R Karl, J Philip Young, Andrew J Montano, Monty A Matthews, Marcy D Bizieff, Alec Nyangao, Edna Mohammed, Hussein Harris, Melissa N Hellerstein, Marc K Rood, Jennifer C Pasiakos, Stefan M |
| description | Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined.
The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit.
This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238).
The study was conducted at Pennington Biomedical Research Center.
Fifty healthy men.
The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding.
Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method.
Mixed-MPS was lower than Pre at Mid and Post (P |
| doi_str_mv | 10.1210/clinem/dgac295 |
| format | article |
| fullrecord | <record><control><sourceid>gale_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_1983048</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A777587418</galeid><sourcerecordid>A777587418</sourcerecordid><originalsourceid>FETCH-LOGICAL-c396t-f17262b0ba46ae5952ce1bbed9d8a28007b72e2dd71931f563f595c050d03b6e3</originalsourceid><addsrcrecordid>eNptkc1LJDEQxYO46Oh69SjBPbfmo9PpHEV0FYS97MLeQjqpjJHpZEgy4Pz3Rlo9SR0Kit-r4tVD6JySK8ooubabEGG-dmtjmRIHaEVVLzpJlTxEK0IY7ZRk_4_RSSkvhNC-F_wIHXMhOBtHtUJw5z3YWnDyuEKpqVTIKQJOEc_hFVw374rdAN7mVCFEXPaxPkMJBZvolmmaAbt9NHOwBbtdDnGNIUJe77EDH2yoP9EPbzYFzj76Kfp3f_f39qF7-vP78fbmqbNcDbXzVLKBTWQy_WBAKMEs0GkCp9xo2EiInCQD5lzzx6kXA_cNskQQR_g0AD9Fl8veZiPo0i6DfbYpxmZRUzVy0o8N-rVAa7MBHaJPNRs7h2L1jZRSjLKn79TVN1QrB81n-5APbf6dwOZUSgavtznMJu81Jfo9K71kpT-yaoKLRbDdTTO4L_wzHP4GfhOSkg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit</title><source>Oxford Journals Online</source><creator>Howard, Emily E ; Shankaran, Mahalakshmi ; Evans, Willian J ; Berryman, Claire E ; Margolis, Lee M ; Lieberman, Harris R ; Karl, J Philip ; Young, Andrew J ; Montano, Monty A ; Matthews, Marcy D ; Bizieff, Alec ; Nyangao, Edna ; Mohammed, Hussein ; Harris, Melissa N ; Hellerstein, Marc K ; Rood, Jennifer C ; Pasiakos, Stefan M</creator><creatorcontrib>Howard, Emily E ; Shankaran, Mahalakshmi ; Evans, Willian J ; Berryman, Claire E ; Margolis, Lee M ; Lieberman, Harris R ; Karl, J Philip ; Young, Andrew J ; Montano, Monty A ; Matthews, Marcy D ; Bizieff, Alec ; Nyangao, Edna ; Mohammed, Hussein ; Harris, Melissa N ; Hellerstein, Marc K ; Rood, Jennifer C ; Pasiakos, Stefan M ; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><description>Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined.
The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit.
This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238).
The study was conducted at Pennington Biomedical Research Center.
Fifty healthy men.
The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding.
Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method.
Mixed-MPS was lower than Pre at Mid and Post (P<0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by two-tailed binomial test at Post (52/67; P<0.05), but not Mid (32/67; P>0.05). Muscle mass was unchanged during energy deficit, but was greater in TEST than PLA during recovery (P<0.05).
The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgac295</identifier><identifier>PMID: 35532889</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Analysis ; Creatine ; Endocrinology & Metabolism ; Heavy water ; Liquid chromatography ; Medical research ; Medicine, Experimental ; Muscles ; Oxandrolone ; Protein biosynthesis ; Testosterone ; Weight loss maintenance</subject><ispartof>The journal of clinical endocrinology and metabolism, 2022-08, Vol.107 (8), p.e3254-e3263</ispartof><rights>Published by Oxford University Press on behalf of the Endocrine Society 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-f17262b0ba46ae5952ce1bbed9d8a28007b72e2dd71931f563f595c050d03b6e3</citedby><cites>FETCH-LOGICAL-c396t-f17262b0ba46ae5952ce1bbed9d8a28007b72e2dd71931f563f595c050d03b6e3</cites><orcidid>0000-0001-7979-1236 ; 0000-0002-0652-1304 ; 0000-0002-5378-5820 ; 0000-0001-5848-2987 ; 0000000158482987 ; 0000000253785820 ; 0000000206521304 ; 0000000179791236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35532889$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1983048$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Howard, Emily E</creatorcontrib><creatorcontrib>Shankaran, Mahalakshmi</creatorcontrib><creatorcontrib>Evans, Willian J</creatorcontrib><creatorcontrib>Berryman, Claire E</creatorcontrib><creatorcontrib>Margolis, Lee M</creatorcontrib><creatorcontrib>Lieberman, Harris R</creatorcontrib><creatorcontrib>Karl, J Philip</creatorcontrib><creatorcontrib>Young, Andrew J</creatorcontrib><creatorcontrib>Montano, Monty A</creatorcontrib><creatorcontrib>Matthews, Marcy D</creatorcontrib><creatorcontrib>Bizieff, Alec</creatorcontrib><creatorcontrib>Nyangao, Edna</creatorcontrib><creatorcontrib>Mohammed, Hussein</creatorcontrib><creatorcontrib>Harris, Melissa N</creatorcontrib><creatorcontrib>Hellerstein, Marc K</creatorcontrib><creatorcontrib>Rood, Jennifer C</creatorcontrib><creatorcontrib>Pasiakos, Stefan M</creatorcontrib><creatorcontrib>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><title>Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined.
The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit.
This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238).
The study was conducted at Pennington Biomedical Research Center.
Fifty healthy men.
The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding.
Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method.
Mixed-MPS was lower than Pre at Mid and Post (P<0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by two-tailed binomial test at Post (52/67; P<0.05), but not Mid (32/67; P>0.05). Muscle mass was unchanged during energy deficit, but was greater in TEST than PLA during recovery (P<0.05).
The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.</description><subject>Analysis</subject><subject>Creatine</subject><subject>Endocrinology & Metabolism</subject><subject>Heavy water</subject><subject>Liquid chromatography</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Muscles</subject><subject>Oxandrolone</subject><subject>Protein biosynthesis</subject><subject>Testosterone</subject><subject>Weight loss maintenance</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNptkc1LJDEQxYO46Oh69SjBPbfmo9PpHEV0FYS97MLeQjqpjJHpZEgy4Pz3Rlo9SR0Kit-r4tVD6JySK8ooubabEGG-dmtjmRIHaEVVLzpJlTxEK0IY7ZRk_4_RSSkvhNC-F_wIHXMhOBtHtUJw5z3YWnDyuEKpqVTIKQJOEc_hFVw374rdAN7mVCFEXPaxPkMJBZvolmmaAbt9NHOwBbtdDnGNIUJe77EDH2yoP9EPbzYFzj76Kfp3f_f39qF7-vP78fbmqbNcDbXzVLKBTWQy_WBAKMEs0GkCp9xo2EiInCQD5lzzx6kXA_cNskQQR_g0AD9Fl8veZiPo0i6DfbYpxmZRUzVy0o8N-rVAa7MBHaJPNRs7h2L1jZRSjLKn79TVN1QrB81n-5APbf6dwOZUSgavtznMJu81Jfo9K71kpT-yaoKLRbDdTTO4L_wzHP4GfhOSkg</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Howard, Emily E</creator><creator>Shankaran, Mahalakshmi</creator><creator>Evans, Willian J</creator><creator>Berryman, Claire E</creator><creator>Margolis, Lee M</creator><creator>Lieberman, Harris R</creator><creator>Karl, J Philip</creator><creator>Young, Andrew J</creator><creator>Montano, Monty A</creator><creator>Matthews, Marcy D</creator><creator>Bizieff, Alec</creator><creator>Nyangao, Edna</creator><creator>Mohammed, Hussein</creator><creator>Harris, Melissa N</creator><creator>Hellerstein, Marc K</creator><creator>Rood, Jennifer C</creator><creator>Pasiakos, Stefan M</creator><general>Oxford University Press</general><general>Oxford University Press - Endocrine Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0001-7979-1236</orcidid><orcidid>https://orcid.org/0000-0002-0652-1304</orcidid><orcidid>https://orcid.org/0000-0002-5378-5820</orcidid><orcidid>https://orcid.org/0000-0001-5848-2987</orcidid><orcidid>https://orcid.org/0000000158482987</orcidid><orcidid>https://orcid.org/0000000253785820</orcidid><orcidid>https://orcid.org/0000000206521304</orcidid><orcidid>https://orcid.org/0000000179791236</orcidid></search><sort><creationdate>20220801</creationdate><title>Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit</title><author>Howard, Emily E ; Shankaran, Mahalakshmi ; Evans, Willian J ; Berryman, Claire E ; Margolis, Lee M ; Lieberman, Harris R ; Karl, J Philip ; Young, Andrew J ; Montano, Monty A ; Matthews, Marcy D ; Bizieff, Alec ; Nyangao, Edna ; Mohammed, Hussein ; Harris, Melissa N ; Hellerstein, Marc K ; Rood, Jennifer C ; Pasiakos, Stefan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-f17262b0ba46ae5952ce1bbed9d8a28007b72e2dd71931f563f595c050d03b6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Creatine</topic><topic>Endocrinology & Metabolism</topic><topic>Heavy water</topic><topic>Liquid chromatography</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Muscles</topic><topic>Oxandrolone</topic><topic>Protein biosynthesis</topic><topic>Testosterone</topic><topic>Weight loss maintenance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Howard, Emily E</creatorcontrib><creatorcontrib>Shankaran, Mahalakshmi</creatorcontrib><creatorcontrib>Evans, Willian J</creatorcontrib><creatorcontrib>Berryman, Claire E</creatorcontrib><creatorcontrib>Margolis, Lee M</creatorcontrib><creatorcontrib>Lieberman, Harris R</creatorcontrib><creatorcontrib>Karl, J Philip</creatorcontrib><creatorcontrib>Young, Andrew J</creatorcontrib><creatorcontrib>Montano, Monty A</creatorcontrib><creatorcontrib>Matthews, Marcy D</creatorcontrib><creatorcontrib>Bizieff, Alec</creatorcontrib><creatorcontrib>Nyangao, Edna</creatorcontrib><creatorcontrib>Mohammed, Hussein</creatorcontrib><creatorcontrib>Harris, Melissa N</creatorcontrib><creatorcontrib>Hellerstein, Marc K</creatorcontrib><creatorcontrib>Rood, Jennifer C</creatorcontrib><creatorcontrib>Pasiakos, Stefan M</creatorcontrib><creatorcontrib>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Howard, Emily E</au><au>Shankaran, Mahalakshmi</au><au>Evans, Willian J</au><au>Berryman, Claire E</au><au>Margolis, Lee M</au><au>Lieberman, Harris R</au><au>Karl, J Philip</au><au>Young, Andrew J</au><au>Montano, Monty A</au><au>Matthews, Marcy D</au><au>Bizieff, Alec</au><au>Nyangao, Edna</au><au>Mohammed, Hussein</au><au>Harris, Melissa N</au><au>Hellerstein, Marc K</au><au>Rood, Jennifer C</au><au>Pasiakos, Stefan M</au><aucorp>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2022-08-01</date><risdate>2022</risdate><volume>107</volume><issue>8</issue><spage>e3254</spage><epage>e3263</epage><pages>e3254-e3263</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined.
The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit.
This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238).
The study was conducted at Pennington Biomedical Research Center.
Fifty healthy men.
The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding.
Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method.
Mixed-MPS was lower than Pre at Mid and Post (P<0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by two-tailed binomial test at Post (52/67; P<0.05), but not Mid (32/67; P>0.05). Muscle mass was unchanged during energy deficit, but was greater in TEST than PLA during recovery (P<0.05).
The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>35532889</pmid><doi>10.1210/clinem/dgac295</doi><orcidid>https://orcid.org/0000-0001-7979-1236</orcidid><orcidid>https://orcid.org/0000-0002-0652-1304</orcidid><orcidid>https://orcid.org/0000-0002-5378-5820</orcidid><orcidid>https://orcid.org/0000-0001-5848-2987</orcidid><orcidid>https://orcid.org/0000000158482987</orcidid><orcidid>https://orcid.org/0000000253785820</orcidid><orcidid>https://orcid.org/0000000206521304</orcidid><orcidid>https://orcid.org/0000000179791236</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The journal of clinical endocrinology and metabolism, 2022-08, Vol.107 (8), p.e3254-e3263 |
| issn | 0021-972X 1945-7197 |
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| recordid | cdi_osti_scitechconnect_1983048 |
| source | Oxford Journals Online |
| subjects | Analysis Creatine Endocrinology & Metabolism Heavy water Liquid chromatography Medical research Medicine, Experimental Muscles Oxandrolone Protein biosynthesis Testosterone Weight loss maintenance |
| title | Effects of testosterone on mixed-muscle protein synthesis and proteome dynamics during energy deficit |
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