Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development
Context Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action...
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| Veröffentlicht in: | European journal of endocrinology 2017-08, Vol.177 (2), p.137-143 |
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| creator | Birzniece, Vita Barrett, P Hugh R Ho, Ken K Y |
| description | Context Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. Aim To investigate whether tamoxifen reduces hepatic VLDL secretion. Design Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H3-leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Results Tamoxifen significantly (P |
| doi_str_mv | 10.1530/EJE-17-0151 |
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Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. Aim To investigate whether tamoxifen reduces hepatic VLDL secretion. Design Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H3-leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Results Tamoxifen significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 ± 7.8% and 29.8 ± 10.2%, respectively. In contrast, EV did not significantly change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly reduced (P < 0.05) GH response to arginine stimulation. Both treatments significantly lowered (P < 0.05) circulating IGF-1. Conclusion Inhibition of VLDL secretion may contribute to the development of fatty liver during tamoxifen therapy. As GH stimulates VLDL secretion, the development of steatosis may arise secondarily from GH insufficiency induced by tamoxifen.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/EJE-17-0151</identifier><identifier>PMID: 28500244</identifier><language>eng</language><publisher>England: Bioscientifica Ltd</publisher><subject>17β-Estradiol ; Aged ; Apolipoprotein B ; Arginine ; Clinical Study ; Estrogen Antagonists - adverse effects ; Estrogen Antagonists - pharmacology ; Fatty liver ; Fatty Liver - blood ; Fatty Liver - chemically induced ; Fatty Liver - diagnosis ; Female ; Growth hormones ; Human Growth Hormone - antagonists & inhibitors ; Human Growth Hormone - blood ; Humans ; Insulin-like growth factor I ; Leucine ; Lipoproteins ; Lipoproteins (very low density) ; Lipoproteins, VLDL - antagonists & inhibitors ; Lipoproteins, VLDL - blood ; Liver - drug effects ; Liver - metabolism ; Low density lipoprotein ; Middle Aged ; Secretion ; Steatosis ; Tamoxifen ; Tamoxifen - adverse effects ; Tamoxifen - pharmacology</subject><ispartof>European journal of endocrinology, 2017-08, Vol.177 (2), p.137-143</ispartof><rights>2017 European Society of Endocrinology</rights><rights>2017 European Society of Endocrinology.</rights><rights>Copyright BioScientifica Ltd. Aug 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b462t-4550cd4af65e7209b76ef0aa0f3090ead93a4a47bbd7dfb78a2710956de698123</citedby><cites>FETCH-LOGICAL-b462t-4550cd4af65e7209b76ef0aa0f3090ead93a4a47bbd7dfb78a2710956de698123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28500244$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Birzniece, Vita</creatorcontrib><creatorcontrib>Barrett, P Hugh R</creatorcontrib><creatorcontrib>Ho, Ken K Y</creatorcontrib><title>Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>Context Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. Aim To investigate whether tamoxifen reduces hepatic VLDL secretion. Design Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H3-leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Results Tamoxifen significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 ± 7.8% and 29.8 ± 10.2%, respectively. In contrast, EV did not significantly change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly reduced (P < 0.05) GH response to arginine stimulation. Both treatments significantly lowered (P < 0.05) circulating IGF-1. Conclusion Inhibition of VLDL secretion may contribute to the development of fatty liver during tamoxifen therapy. As GH stimulates VLDL secretion, the development of steatosis may arise secondarily from GH insufficiency induced by tamoxifen.</description><subject>17β-Estradiol</subject><subject>Aged</subject><subject>Apolipoprotein B</subject><subject>Arginine</subject><subject>Clinical Study</subject><subject>Estrogen Antagonists - adverse effects</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Fatty liver</subject><subject>Fatty Liver - blood</subject><subject>Fatty Liver - chemically induced</subject><subject>Fatty Liver - diagnosis</subject><subject>Female</subject><subject>Growth hormones</subject><subject>Human Growth Hormone - antagonists & inhibitors</subject><subject>Human Growth Hormone - blood</subject><subject>Humans</subject><subject>Insulin-like growth factor I</subject><subject>Leucine</subject><subject>Lipoproteins</subject><subject>Lipoproteins (very low density)</subject><subject>Lipoproteins, VLDL - antagonists & inhibitors</subject><subject>Lipoproteins, VLDL - blood</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Low density lipoprotein</subject><subject>Middle Aged</subject><subject>Secretion</subject><subject>Steatosis</subject><subject>Tamoxifen</subject><subject>Tamoxifen - adverse effects</subject><subject>Tamoxifen - pharmacology</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EotuFE3dkiQtSFRgndhxzq8rSFq3EpSBulmOPVVdJHOwE2n-PyxYOPXCa0dOnp5n3CHnF4B0TDbzffd5VTFbABHtCNoxLVbVd8_0p2UAHvOItb47Icc43AKzs8Jwc1Z0AqDnfkHxlxngbPE40oVstZnqNs1mCpd_2H_d0TrGoS4gTNZOj5xc0o034RwgT_RVHnD5QQ-eYc-gHpCPaazOFPFIfE80LmiXmkKnDnzjEueDLC_LMmyHjy4e5JV8_7a7OLqr9l_PLs9N91fO2XiouBFjHjW8FyhpUL1v0YAz4BhSgcaox3HDZ904638vO1JKBEq3DVnWsbrbk7cG3PPFjxbzoMWSLw2AmjGvWrFOKMdkIVdA3j9CbuKapXKdraCQIJkumW3JyoGwq7yb0ek5hNOlOM9D3XejShWZS33dR6NcPnms_ovvH_g2_AOwA9CFmG0oywQdr_mv6G8l6lKc</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Birzniece, Vita</creator><creator>Barrett, P Hugh R</creator><creator>Ho, Ken K Y</creator><general>Bioscientifica Ltd</general><general>Oxford University Press</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201708</creationdate><title>Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development</title><author>Birzniece, Vita ; Barrett, P Hugh R ; Ho, Ken K Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b462t-4550cd4af65e7209b76ef0aa0f3090ead93a4a47bbd7dfb78a2710956de698123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>17β-Estradiol</topic><topic>Aged</topic><topic>Apolipoprotein B</topic><topic>Arginine</topic><topic>Clinical Study</topic><topic>Estrogen Antagonists - adverse effects</topic><topic>Estrogen Antagonists - pharmacology</topic><topic>Fatty liver</topic><topic>Fatty Liver - blood</topic><topic>Fatty Liver - chemically induced</topic><topic>Fatty Liver - diagnosis</topic><topic>Female</topic><topic>Growth hormones</topic><topic>Human Growth Hormone - antagonists & inhibitors</topic><topic>Human Growth Hormone - blood</topic><topic>Humans</topic><topic>Insulin-like growth factor I</topic><topic>Leucine</topic><topic>Lipoproteins</topic><topic>Lipoproteins (very low density)</topic><topic>Lipoproteins, VLDL - antagonists & inhibitors</topic><topic>Lipoproteins, VLDL - blood</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Low density lipoprotein</topic><topic>Middle Aged</topic><topic>Secretion</topic><topic>Steatosis</topic><topic>Tamoxifen</topic><topic>Tamoxifen - adverse effects</topic><topic>Tamoxifen - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Birzniece, Vita</creatorcontrib><creatorcontrib>Barrett, P Hugh R</creatorcontrib><creatorcontrib>Ho, Ken K Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Birzniece, Vita</au><au>Barrett, P Hugh R</au><au>Ho, Ken K Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2017-08</date><risdate>2017</risdate><volume>177</volume><issue>2</issue><spage>137</spage><epage>143</epage><pages>137-143</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>Context Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. Aim To investigate whether tamoxifen reduces hepatic VLDL secretion. Design Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H3-leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Results Tamoxifen significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 ± 7.8% and 29.8 ± 10.2%, respectively. In contrast, EV did not significantly change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly reduced (P < 0.05) GH response to arginine stimulation. Both treatments significantly lowered (P < 0.05) circulating IGF-1. Conclusion Inhibition of VLDL secretion may contribute to the development of fatty liver during tamoxifen therapy. As GH stimulates VLDL secretion, the development of steatosis may arise secondarily from GH insufficiency induced by tamoxifen.</abstract><cop>England</cop><pub>Bioscientifica Ltd</pub><pmid>28500244</pmid><doi>10.1530/EJE-17-0151</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | 17β-Estradiol Aged Apolipoprotein B Arginine Clinical Study Estrogen Antagonists - adverse effects Estrogen Antagonists - pharmacology Fatty liver Fatty Liver - blood Fatty Liver - chemically induced Fatty Liver - diagnosis Female Growth hormones Human Growth Hormone - antagonists & inhibitors Human Growth Hormone - blood Humans Insulin-like growth factor I Leucine Lipoproteins Lipoproteins (very low density) Lipoproteins, VLDL - antagonists & inhibitors Lipoproteins, VLDL - blood Liver - drug effects Liver - metabolism Low density lipoprotein Middle Aged Secretion Steatosis Tamoxifen Tamoxifen - adverse effects Tamoxifen - pharmacology |
| title | Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development |
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