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
Hauptverfasser: van der Sluis, Ronald J., Depuydt, Marie A.C., Verwilligen, Robin A.F., Hoekstra, Menno, Van Eck, Miranda
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container_start_page 21
container_title Molecular and cellular endocrinology
container_volume 490
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 
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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 &lt; 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 &lt; 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><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. 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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><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. ; 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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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