Elimination of adrenocortical apolipoprotein E production does not impact glucocorticoid output in wild-type mice
Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted...
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Veröffentlicht in: | Molecular and cellular endocrinology 2019-06, Vol.490, p.21-27 |
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creator | van der Sluis, Ronald J. Depuydt, Marie A.C. Verwilligen, Robin A.F. Hoekstra, Menno Van Eck, Miranda |
description | Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted into adrenalectomized wild-type mice. Adrenal APOE deficiency did not impact adrenal total cholesterol levels. Importantly, the ability of the two adrenal types to produce glucocorticoids was also not different as judged from the similar plasma corticosterone levels. Adrenal mRNA expression levels of HMG-CoA reductase and the LDL receptor were decreased by respectively 72% (p |
doi_str_mv | 10.1016/j.mce.2019.04.001 |
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In conclusion, our studies show that elimination of adrenocortical APOE production does not impact glucocorticoid output in wild-type mice.
•Adrenal APOE alters cellular cholesterol homeostasis.•Adrenal APOE does not interfere in steroidogenesis.•Adrenal APOE deficiency does not impact plasma cholesterol levels.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2019.04.001</identifier><identifier>PMID: 30953750</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Adrenal ; Adrenal Cortex - drug effects ; Adrenal Cortex - metabolism ; Adrenal transplantation ; Animals ; Apolipoprotein E ; Apolipoproteins E - biosynthesis ; Apolipoproteins E - deficiency ; Cholesterol - metabolism ; Endoplasmic Reticulum Stress - drug effects ; Glucocorticoid ; Glucocorticoids - pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; Organ Specificity ; RNA, Messenger - genetics ; RNA, Messenger - metabolism</subject><ispartof>Molecular and cellular endocrinology, 2019-06, Vol.490, p.21-27</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-8efc0bd30dc07730c51dbdc17c823cf5ec065ee06c94aca8d6473c888a2440e63</citedby><cites>FETCH-LOGICAL-c353t-8efc0bd30dc07730c51dbdc17c823cf5ec065ee06c94aca8d6473c888a2440e63</cites><orcidid>0000-0002-3435-8356 ; 0000-0002-7174-1952 ; 0000-0001-7463-2893</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2019.04.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30953750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Sluis, Ronald J.</creatorcontrib><creatorcontrib>Depuydt, Marie A.C.</creatorcontrib><creatorcontrib>Verwilligen, Robin A.F.</creatorcontrib><creatorcontrib>Hoekstra, Menno</creatorcontrib><creatorcontrib>Van Eck, Miranda</creatorcontrib><title>Elimination of adrenocortical apolipoprotein E production does not impact glucocorticoid output in wild-type mice</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted into adrenalectomized wild-type mice. Adrenal APOE deficiency did not impact adrenal total cholesterol levels. Importantly, the ability of the two adrenal types to produce glucocorticoids was also not different as judged from the similar plasma corticosterone levels. Adrenal mRNA expression levels of HMG-CoA reductase and the LDL receptor were decreased by respectively 72% (p < 0.01) and 65% (p = 0.07), suggesting that cholesterol acquisition pathways were inhibited to possibly compensate the lack of APOE. In support, a parallel increase in the expression level of the cholesterol accumulation-associated ER stress marker CHOP was detected (+117%; p < 0.05).
In conclusion, our studies show that elimination of adrenocortical APOE production does not impact glucocorticoid output in wild-type mice.
•Adrenal APOE alters cellular cholesterol homeostasis.•Adrenal APOE does not interfere in steroidogenesis.•Adrenal APOE deficiency does not impact plasma cholesterol levels.</description><subject>Adrenal</subject><subject>Adrenal Cortex - drug effects</subject><subject>Adrenal Cortex - metabolism</subject><subject>Adrenal transplantation</subject><subject>Animals</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - biosynthesis</subject><subject>Apolipoproteins E - deficiency</subject><subject>Cholesterol - metabolism</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Glucocorticoid</subject><subject>Glucocorticoids - pharmacology</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Organ Specificity</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi1ERZfCA3BBPnJJGNtJ7IgTqrYFqRKXcra84wnyKolT2wH17cmyC0dOHsnf_2vmY-ydgFqA6D4e6wmpliD6GpoaQLxgO2G0rAy0-iXbgQJVaQn6mr3O-QgAupXmFbtW0LdKt7BjT_sxTGF2JcSZx4E7n2iOGFMJ6EbuljiGJS4pFgoz3_Nt8iv-oX2kzOdYeJgWh4X_GFe8JGPwPK5lWbfPmf8Ko6_K80J8Ckhv2NXgxkxvL-8N-363f7z9Uj18u_96-_mhQtWqUhkaEA5egUfQWgG2wh88Co1GKhxaQuhaIuiwbxw647tGKzTGONk0QJ26YR_OvdvKTyvlYqeQkcbRzRTXbKWEpjO97E-oOKOYYs6JBrukMLn0bAXYk2l7tJtpezJtobGb6S3z_lK_Hiby_xJ_1W7ApzNA25E_AyWbMdCM5EMiLNbH8J_63292kUU</recordid><startdate>20190615</startdate><enddate>20190615</enddate><creator>van der Sluis, Ronald J.</creator><creator>Depuydt, Marie A.C.</creator><creator>Verwilligen, Robin A.F.</creator><creator>Hoekstra, Menno</creator><creator>Van Eck, Miranda</creator><general>Elsevier B.V</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><orcidid>https://orcid.org/0000-0002-3435-8356</orcidid><orcidid>https://orcid.org/0000-0002-7174-1952</orcidid><orcidid>https://orcid.org/0000-0001-7463-2893</orcidid></search><sort><creationdate>20190615</creationdate><title>Elimination of adrenocortical apolipoprotein E production does not impact glucocorticoid output in wild-type mice</title><author>van der Sluis, Ronald J. ; Depuydt, Marie A.C. ; Verwilligen, Robin A.F. ; Hoekstra, Menno ; Van Eck, Miranda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-8efc0bd30dc07730c51dbdc17c823cf5ec065ee06c94aca8d6473c888a2440e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adrenal</topic><topic>Adrenal Cortex - drug effects</topic><topic>Adrenal Cortex - metabolism</topic><topic>Adrenal transplantation</topic><topic>Animals</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins E - biosynthesis</topic><topic>Apolipoproteins E - deficiency</topic><topic>Cholesterol - metabolism</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Glucocorticoid</topic><topic>Glucocorticoids - pharmacology</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Organ Specificity</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Sluis, Ronald J.</creatorcontrib><creatorcontrib>Depuydt, Marie A.C.</creatorcontrib><creatorcontrib>Verwilligen, Robin A.F.</creatorcontrib><creatorcontrib>Hoekstra, Menno</creatorcontrib><creatorcontrib>Van Eck, Miranda</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><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Sluis, Ronald J.</au><au>Depuydt, Marie A.C.</au><au>Verwilligen, Robin A.F.</au><au>Hoekstra, Menno</au><au>Van Eck, Miranda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elimination of adrenocortical apolipoprotein E production does not impact glucocorticoid output in wild-type mice</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2019-06-15</date><risdate>2019</risdate><volume>490</volume><spage>21</spage><epage>27</epage><pages>21-27</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted into adrenalectomized wild-type mice. Adrenal APOE deficiency did not impact adrenal total cholesterol levels. Importantly, the ability of the two adrenal types to produce glucocorticoids was also not different as judged from the similar plasma corticosterone levels. Adrenal mRNA expression levels of HMG-CoA reductase and the LDL receptor were decreased by respectively 72% (p < 0.01) and 65% (p = 0.07), suggesting that cholesterol acquisition pathways were inhibited to possibly compensate the lack of APOE. In support, a parallel increase in the expression level of the cholesterol accumulation-associated ER stress marker CHOP was detected (+117%; p < 0.05).
In conclusion, our studies show that elimination of adrenocortical APOE production does not impact glucocorticoid output in wild-type mice.
•Adrenal APOE alters cellular cholesterol homeostasis.•Adrenal APOE does not interfere in steroidogenesis.•Adrenal APOE deficiency does not impact plasma cholesterol levels.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30953750</pmid><doi>10.1016/j.mce.2019.04.001</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3435-8356</orcidid><orcidid>https://orcid.org/0000-0002-7174-1952</orcidid><orcidid>https://orcid.org/0000-0001-7463-2893</orcidid></addata></record> |
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subjects | Adrenal Adrenal Cortex - drug effects Adrenal Cortex - metabolism Adrenal transplantation Animals Apolipoprotein E Apolipoproteins E - biosynthesis Apolipoproteins E - deficiency Cholesterol - metabolism Endoplasmic Reticulum Stress - drug effects Glucocorticoid Glucocorticoids - pharmacology Mice, Inbred C57BL Mice, Knockout Organ Specificity RNA, Messenger - genetics RNA, Messenger - metabolism |
title | Elimination of adrenocortical apolipoprotein E production does not impact glucocorticoid output in wild-type mice |
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