Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis
This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were qua...
Gespeichert in:
| Veröffentlicht in: | Molecular and cellular endocrinology 2002-08, Vol.194 (1), p.39-50 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 50 |
|---|---|
| container_issue | 1 |
| container_start_page | 39 |
| container_title | Molecular and cellular endocrinology |
| container_volume | 194 |
| creator | Drewett, James G Adams-Hays, Robin L Ho, Begonia Y Hegge, David J |
| description | This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3β-hydroxy-Δ
5-steroid dehydrogenase inhibitor, 2α-cyano-17β-hydroxy-4,4′,17α-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-
N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin- and 22α-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-
a]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole did not inhibit steroidogenesis. The IC
50 for effects of free NO on CYP11A1 was potent and in the 0.4–2 μM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation. |
| doi_str_mv | 10.1016/S0303-7207(02)00214-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72106859</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0303720702002149</els_id><sourcerecordid>72106859</sourcerecordid><originalsourceid>FETCH-LOGICAL-c361t-1392e21b4dfd0c6b9dafd28776c91ea2e3da0484a1074d1486ae7f5d50c872733</originalsourceid><addsrcrecordid>eNqFkElPwzAQhS0EglL4CaCcEBwCY2dxckKoYpMqkFjOlmtPyqAsxXYR5deTLoIjp3f53jzNx9gRh3MOPL94hgSSWAqQpyDOAARP43KLDXghRVxAJrfZ4BfZY_vevwOAzESxy_a4EKkAkQ_Y0wMFRybqvshiNOsCtqFeRNS-0YSCj8IbRk4HjGtqKFA7jbD9XjQ69B0fcNaTy3Qd2W6KLXryB2yn0rXHw00O2evN9cvoLh4_3t6PrsaxSXIeYp6UAgWfpLayYPJJaXVlRSFlbkqOWmBiNaRFqjnI1PK0yDXKKrMZmP5FmSRDdrK-O3Pdxxx9UA15g3WtW-zmXknBIS-ysgezNWhc573DSs0cNdotFAe1lKlWMtXSlAKhVjLVsne8GZhPGrR_rY29HrhcA9i_-UnolDeErUFLDk1QtqN_Jn4A06GEwg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72106859</pqid></control><display><type>article</type><title>Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Drewett, James G ; Adams-Hays, Robin L ; Ho, Begonia Y ; Hegge, David J</creator><creatorcontrib>Drewett, James G ; Adams-Hays, Robin L ; Ho, Begonia Y ; Hegge, David J</creatorcontrib><description>This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3β-hydroxy-Δ
5-steroid dehydrogenase inhibitor, 2α-cyano-17β-hydroxy-4,4′,17α-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-
N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin- and 22α-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-
a]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole did not inhibit steroidogenesis. The IC
50 for effects of free NO on CYP11A1 was potent and in the 0.4–2 μM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/S0303-7207(02)00214-9</identifier><identifier>PMID: 12242026</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Adrenocortical steroidogenesis (human) ; Aldosterone ; Animals ; Catalysis - drug effects ; Cholesterol Side-Chain Cleavage Enzyme - antagonists & inhibitors ; Cholesterol Side-Chain Cleavage Enzyme - metabolism ; COS Cells ; Cyclic GMP - analysis ; Cytochrome P450 ; Guanylate Cyclase - drug effects ; Guanylate Cyclase - metabolism ; Guanylyl cyclase ; Humans ; Hydrazines - pharmacology ; Mice ; Mitochondrial Proteins ; Nitric oxide ; Nitric Oxide - physiology ; Nitric Oxide Donors - pharmacology ; Nitroso Compounds ; PC12 Cells ; Pregnenolone ; Pregnenolone - biosynthesis ; Rats ; Steroids - biosynthesis ; Transfection</subject><ispartof>Molecular and cellular endocrinology, 2002-08, Vol.194 (1), p.39-50</ispartof><rights>2002 Elsevier Science Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-1392e21b4dfd0c6b9dafd28776c91ea2e3da0484a1074d1486ae7f5d50c872733</citedby><cites>FETCH-LOGICAL-c361t-1392e21b4dfd0c6b9dafd28776c91ea2e3da0484a1074d1486ae7f5d50c872733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0303-7207(02)00214-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12242026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Drewett, James G</creatorcontrib><creatorcontrib>Adams-Hays, Robin L</creatorcontrib><creatorcontrib>Ho, Begonia Y</creatorcontrib><creatorcontrib>Hegge, David J</creatorcontrib><title>Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3β-hydroxy-Δ
5-steroid dehydrogenase inhibitor, 2α-cyano-17β-hydroxy-4,4′,17α-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-
N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin- and 22α-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-
a]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole did not inhibit steroidogenesis. The IC
50 for effects of free NO on CYP11A1 was potent and in the 0.4–2 μM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation.</description><subject>Adrenocortical steroidogenesis (human)</subject><subject>Aldosterone</subject><subject>Animals</subject><subject>Catalysis - drug effects</subject><subject>Cholesterol Side-Chain Cleavage Enzyme - antagonists & inhibitors</subject><subject>Cholesterol Side-Chain Cleavage Enzyme - metabolism</subject><subject>COS Cells</subject><subject>Cyclic GMP - analysis</subject><subject>Cytochrome P450</subject><subject>Guanylate Cyclase - drug effects</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Guanylyl cyclase</subject><subject>Humans</subject><subject>Hydrazines - pharmacology</subject><subject>Mice</subject><subject>Mitochondrial Proteins</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - physiology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroso Compounds</subject><subject>PC12 Cells</subject><subject>Pregnenolone</subject><subject>Pregnenolone - biosynthesis</subject><subject>Rats</subject><subject>Steroids - biosynthesis</subject><subject>Transfection</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkElPwzAQhS0EglL4CaCcEBwCY2dxckKoYpMqkFjOlmtPyqAsxXYR5deTLoIjp3f53jzNx9gRh3MOPL94hgSSWAqQpyDOAARP43KLDXghRVxAJrfZ4BfZY_vevwOAzESxy_a4EKkAkQ_Y0wMFRybqvshiNOsCtqFeRNS-0YSCj8IbRk4HjGtqKFA7jbD9XjQ69B0fcNaTy3Qd2W6KLXryB2yn0rXHw00O2evN9cvoLh4_3t6PrsaxSXIeYp6UAgWfpLayYPJJaXVlRSFlbkqOWmBiNaRFqjnI1PK0yDXKKrMZmP5FmSRDdrK-O3Pdxxx9UA15g3WtW-zmXknBIS-ysgezNWhc573DSs0cNdotFAe1lKlWMtXSlAKhVjLVsne8GZhPGrR_rY29HrhcA9i_-UnolDeErUFLDk1QtqN_Jn4A06GEwg</recordid><startdate>20020830</startdate><enddate>20020830</enddate><creator>Drewett, James G</creator><creator>Adams-Hays, Robin L</creator><creator>Ho, Begonia Y</creator><creator>Hegge, David J</creator><general>Elsevier Ireland Ltd</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></search><sort><creationdate>20020830</creationdate><title>Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis</title><author>Drewett, James G ; Adams-Hays, Robin L ; Ho, Begonia Y ; Hegge, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-1392e21b4dfd0c6b9dafd28776c91ea2e3da0484a1074d1486ae7f5d50c872733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adrenocortical steroidogenesis (human)</topic><topic>Aldosterone</topic><topic>Animals</topic><topic>Catalysis - drug effects</topic><topic>Cholesterol Side-Chain Cleavage Enzyme - antagonists & inhibitors</topic><topic>Cholesterol Side-Chain Cleavage Enzyme - metabolism</topic><topic>COS Cells</topic><topic>Cyclic GMP - analysis</topic><topic>Cytochrome P450</topic><topic>Guanylate Cyclase - drug effects</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Guanylyl cyclase</topic><topic>Humans</topic><topic>Hydrazines - pharmacology</topic><topic>Mice</topic><topic>Mitochondrial Proteins</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - physiology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroso Compounds</topic><topic>PC12 Cells</topic><topic>Pregnenolone</topic><topic>Pregnenolone - biosynthesis</topic><topic>Rats</topic><topic>Steroids - biosynthesis</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Drewett, James G</creatorcontrib><creatorcontrib>Adams-Hays, Robin L</creatorcontrib><creatorcontrib>Ho, Begonia Y</creatorcontrib><creatorcontrib>Hegge, David J</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>Drewett, James G</au><au>Adams-Hays, Robin L</au><au>Ho, Begonia Y</au><au>Hegge, David J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2002-08-30</date><risdate>2002</risdate><volume>194</volume><issue>1</issue><spage>39</spage><epage>50</epage><pages>39-50</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3β-hydroxy-Δ
5-steroid dehydrogenase inhibitor, 2α-cyano-17β-hydroxy-4,4′,17α-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-
N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin- and 22α-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-
a]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole did not inhibit steroidogenesis. The IC
50 for effects of free NO on CYP11A1 was potent and in the 0.4–2 μM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>12242026</pmid><doi>10.1016/S0303-7207(02)00214-9</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0303-7207 |
| ispartof | Molecular and cellular endocrinology, 2002-08, Vol.194 (1), p.39-50 |
| issn | 0303-7207 1872-8057 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72106859 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adrenocortical steroidogenesis (human) Aldosterone Animals Catalysis - drug effects Cholesterol Side-Chain Cleavage Enzyme - antagonists & inhibitors Cholesterol Side-Chain Cleavage Enzyme - metabolism COS Cells Cyclic GMP - analysis Cytochrome P450 Guanylate Cyclase - drug effects Guanylate Cyclase - metabolism Guanylyl cyclase Humans Hydrazines - pharmacology Mice Mitochondrial Proteins Nitric oxide Nitric Oxide - physiology Nitric Oxide Donors - pharmacology Nitroso Compounds PC12 Cells Pregnenolone Pregnenolone - biosynthesis Rats Steroids - biosynthesis Transfection |
| title | Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T15%3A45%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nitric%20oxide%20potently%20inhibits%20the%20rate-limiting%20enzymatic%20step%20in%20steroidogenesis&rft.jtitle=Molecular%20and%20cellular%20endocrinology&rft.au=Drewett,%20James%20G&rft.date=2002-08-30&rft.volume=194&rft.issue=1&rft.spage=39&rft.epage=50&rft.pages=39-50&rft.issn=0303-7207&rft.eissn=1872-8057&rft_id=info:doi/10.1016/S0303-7207(02)00214-9&rft_dat=%3Cproquest_cross%3E72106859%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=72106859&rft_id=info:pmid/12242026&rft_els_id=S0303720702002149&rfr_iscdi=true |