Stress-Induced Elevations of γ-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain
A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAAin the...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-05, Vol.88 (10), p.4553-4557 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Purdy, Robert H. Morrow, A. Leslie Moore, Perry H. Paul, Steven M. |
| description | A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAAin the central nervous system. With specific radioimmunoassays, rapid (3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAAreceptor function. |
| doi_str_mv | 10.1073/pnas.88.10.4553 |
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Leslie ; Moore, Perry H. ; Paul, Steven M.</creator><creatorcontrib>Purdy, Robert H. ; Morrow, A. Leslie ; Moore, Perry H. ; Paul, Steven M.</creatorcontrib><description>A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAAin the central nervous system. With specific radioimmunoassays, rapid (<5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swim stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (>3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAAreceptor function.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.10.4553</identifier><identifier>PMID: 1852011</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Adrenalectomy ; Animals ; Biochemistry and metabolism ; Biological and medical sciences ; Blood plasma ; Brain ; Brain - metabolism ; Central nervous system ; Cerebral cortex ; Cerebral Cortex - metabolism ; Desoxycorticosterone - analogs & derivatives ; Fundamental and applied biological sciences. Psychology ; Hypothalamus ; Hypothalamus - metabolism ; Ligands ; Male ; Male animals ; Pregnanolone - analogs & derivatives ; Pregnanolone - blood ; Pregnanolone - metabolism ; Rats ; Rats, Inbred Strains ; Receptors ; Receptors, GABA-A - metabolism ; steroid hormones ; Steroid metabolism ; Steroids ; stress ; Stress, Physiological - metabolism ; Swimming ; Vertebrates: nervous system and sense organs</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-05, Vol.88 (10), p.4553-4557</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-663188a23870e9c1e48c4229f43aaef43ecf7aa67ad046d67e61b41eb97bbeff3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/10.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2357084$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2357084$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19747576$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1852011$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Purdy, Robert H.</creatorcontrib><creatorcontrib>Morrow, A. Leslie</creatorcontrib><creatorcontrib>Moore, Perry H.</creatorcontrib><creatorcontrib>Paul, Steven M.</creatorcontrib><title>Stress-Induced Elevations of γ-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAAin the central nervous system. With specific radioimmunoassays, rapid (<5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swim stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (>3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAAreceptor function.</description><subject>Adrenalectomy</subject><subject>Animals</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Blood plasma</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Central nervous system</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - metabolism</subject><subject>Desoxycorticosterone - analogs & derivatives</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hypothalamus</subject><subject>Hypothalamus - metabolism</subject><subject>Ligands</subject><subject>Male</subject><subject>Male animals</subject><subject>Pregnanolone - analogs & derivatives</subject><subject>Pregnanolone - blood</subject><subject>Pregnanolone - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors</subject><subject>Receptors, GABA-A - metabolism</subject><subject>steroid hormones</subject><subject>Steroid metabolism</subject><subject>Steroids</subject><subject>stress</subject><subject>Stress, Physiological - metabolism</subject><subject>Swimming</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAURi0EKtPCmg0gb4BVpnbiX4nNUBWoVAmpLWvLcW6oq0yS2s6Iea6-B8-EoxlauoGNrevvXF9bB6FXlCwpkdXx2Nu4VCoXS8Z59QQtKNG0EEyTp2hBSCkLxUr2HB3GeEMI0VyRA3RAFS8JpQvkLlOAGIuzvpkcNPi0g41NfugjHlr8665YrX0_1FPaBu_wyvkGX21HwCt8AQ7GNIQinya_AXyZIAy-idj3OF0DvrAJfwrW9y_Qs9Z2EV7u9yP0_fPp1cnX4vzbl7OT1XnhuNKpEKKiStmyUpKAdhSYcqwsdcsqayGv4FpprZC2IUw0QoKgNaNQa1nX0LbVEfq4u3ec6jU0DvoUbGfG4Nc2bM1gvXmc9P7a_Bg2hlOhdW5_v28Pw-0EMZm1jw66zvYwTNEowoUWnPwXpFxnF7LM4PEOdGGIMUB7_xZKzKzPzPqMUnM968sdb_7-wgO_85Xzd_vcRme7Ntje-fiAackklyJzb_fcPOBP_GjQh38Cpp26LsHPlMnXO_ImZtv3aFlxSRSrfgPeVMaV</recordid><startdate>19910515</startdate><enddate>19910515</enddate><creator>Purdy, Robert H.</creator><creator>Morrow, A. Leslie</creator><creator>Moore, Perry H.</creator><creator>Paul, Steven M.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19910515</creationdate><title>Stress-Induced Elevations of γ-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain</title><author>Purdy, Robert H. ; Morrow, A. Leslie ; Moore, Perry H. ; Paul, Steven M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-663188a23870e9c1e48c4229f43aaef43ecf7aa67ad046d67e61b41eb97bbeff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Adrenalectomy</topic><topic>Animals</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Blood plasma</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Central nervous system</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - metabolism</topic><topic>Desoxycorticosterone - analogs & derivatives</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hypothalamus</topic><topic>Hypothalamus - metabolism</topic><topic>Ligands</topic><topic>Male</topic><topic>Male animals</topic><topic>Pregnanolone - analogs & derivatives</topic><topic>Pregnanolone - blood</topic><topic>Pregnanolone - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors</topic><topic>Receptors, GABA-A - metabolism</topic><topic>steroid hormones</topic><topic>Steroid metabolism</topic><topic>Steroids</topic><topic>stress</topic><topic>Stress, Physiological - metabolism</topic><topic>Swimming</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Purdy, Robert H.</creatorcontrib><creatorcontrib>Morrow, A. Leslie</creatorcontrib><creatorcontrib>Moore, Perry H.</creatorcontrib><creatorcontrib>Paul, Steven M.</creatorcontrib><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>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Purdy, Robert H.</au><au>Morrow, A. Leslie</au><au>Moore, Perry H.</au><au>Paul, Steven M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stress-Induced Elevations of γ-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-05-15</date><risdate>1991</risdate><volume>88</volume><issue>10</issue><spage>4553</spage><epage>4557</epage><pages>4553-4557</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAAin the central nervous system. With specific radioimmunoassays, rapid (<5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swim stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (>3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAAreceptor function.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1852011</pmid><doi>10.1073/pnas.88.10.4553</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adrenalectomy Animals Biochemistry and metabolism Biological and medical sciences Blood plasma Brain Brain - metabolism Central nervous system Cerebral cortex Cerebral Cortex - metabolism Desoxycorticosterone - analogs & derivatives Fundamental and applied biological sciences. Psychology Hypothalamus Hypothalamus - metabolism Ligands Male Male animals Pregnanolone - analogs & derivatives Pregnanolone - blood Pregnanolone - metabolism Rats Rats, Inbred Strains Receptors Receptors, GABA-A - metabolism steroid hormones Steroid metabolism Steroids stress Stress, Physiological - metabolism Swimming Vertebrates: nervous system and sense organs |
| title | Stress-Induced Elevations of γ-Aminobutyric Acid Type A Receptor- Active Steroids in the Rat Brain |
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