19-Hydroxylation of Androgens in the Rat Brain
Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successiv...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1985-05, Vol.82 (9), p.2728-2730 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Hahn, Elliot F. Miyairi, Shinichi Fishman, Jack |
| description | Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions. |
| doi_str_mv | 10.1073/pnas.82.9.2728 |
| format | Article |
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The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.82.9.2728</identifier><identifier>PMID: 3857612</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Androgens ; Androgens - metabolism ; Androstenedione - analogs & derivatives ; Androstenedione - biosynthesis ; Androstenedione - metabolism ; Animals ; Biochemistry ; Biological and medical sciences ; Brain ; Brain - metabolism ; Cell physiology ; Central nervous system ; Endocrinology ; Estrogens ; Estrogens - biosynthesis ; Female ; Fundamental and applied biological sciences. Psychology ; Hormonal regulation ; Human sexual behavior ; Humans ; Hydroxylation ; In Vitro Techniques ; Male ; Molecular and cellular biology ; Placenta ; Placenta - metabolism ; Pregnancy ; Rats ; Steroids</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1985-05, Vol.82 (9), p.2728-2730</ispartof><rights>1985 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-53c289f50af13b9951abe657213a2f6b1a7387a488230aeeb4fc09707fbffdf63</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/82/9.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25250$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25250$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=9147291$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3857612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hahn, Elliot F.</creatorcontrib><creatorcontrib>Miyairi, Shinichi</creatorcontrib><creatorcontrib>Fishman, Jack</creatorcontrib><title>19-Hydroxylation of Androgens 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>Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions.</description><subject>Androgens</subject><subject>Androgens - metabolism</subject><subject>Androstenedione - analogs & derivatives</subject><subject>Androstenedione - biosynthesis</subject><subject>Androstenedione - metabolism</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Cell physiology</subject><subject>Central nervous system</subject><subject>Endocrinology</subject><subject>Estrogens</subject><subject>Estrogens - biosynthesis</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormonal regulation</subject><subject>Human sexual behavior</subject><subject>Humans</subject><subject>Hydroxylation</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Molecular and cellular biology</subject><subject>Placenta</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Rats</subject><subject>Steroids</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEFr3DAQhUVoSTdprzkUCj6E3OyOJMuSDj0kIU0KgUJpz2LslRIHr7SVtCH772OzW7OBngbme2_e8Ag5o1BRkPzr2mOqFKt0xSRTR2RBQdOyqTW8IwsAJktVs_oDOUnpCQC0UHBMjrkSsqFsQSqqy7vtMoaX7YC5D74Irrj04-LB-lT0vsiPtviFubiK2PuP5L3DIdlP-3lK_ny_-X19V97_vP1xfXlfdrUSuRS8Y0o7Aegob7UWFFvbCMkoR-aalqLkSmKtFOOA1ra160BLkK51bukafkq-7e6uN-3KLjvrc8TBrGO_wrg1AXvzlvj-0TyEZ8O1bLga_Rd7fwx_NzZls-pTZ4cBvQ2bZGQDGqSYgqqdsIshpWjdnEHBTAWbqWCjmNFmKng0fDn8bJbvGx35-Z5j6nBwEX3Xp1mmaS2ZpgcPTuf_0TnGuM0wZPuSD_L-Kxz55x1_SjnEWcAEE8BfARzlo8w</recordid><startdate>19850501</startdate><enddate>19850501</enddate><creator>Hahn, Elliot F.</creator><creator>Miyairi, Shinichi</creator><creator>Fishman, Jack</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19850501</creationdate><title>19-Hydroxylation of Androgens in the Rat Brain</title><author>Hahn, Elliot F. ; Miyairi, Shinichi ; Fishman, Jack</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-53c289f50af13b9951abe657213a2f6b1a7387a488230aeeb4fc09707fbffdf63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Androgens</topic><topic>Androgens - metabolism</topic><topic>Androstenedione - analogs & derivatives</topic><topic>Androstenedione - biosynthesis</topic><topic>Androstenedione - metabolism</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Cell physiology</topic><topic>Central nervous system</topic><topic>Endocrinology</topic><topic>Estrogens</topic><topic>Estrogens - biosynthesis</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormonal regulation</topic><topic>Human sexual behavior</topic><topic>Humans</topic><topic>Hydroxylation</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Molecular and cellular biology</topic><topic>Placenta</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Rats</topic><topic>Steroids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hahn, Elliot F.</creatorcontrib><creatorcontrib>Miyairi, Shinichi</creatorcontrib><creatorcontrib>Fishman, Jack</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>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>Hahn, Elliot F.</au><au>Miyairi, Shinichi</au><au>Fishman, Jack</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>19-Hydroxylation of Androgens 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>1985-05-01</date><risdate>1985</risdate><volume>82</volume><issue>9</issue><spage>2728</spage><epage>2730</epage><pages>2728-2730</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>3857612</pmid><doi>10.1073/pnas.82.9.2728</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Androgens Androgens - metabolism Androstenedione - analogs & derivatives Androstenedione - biosynthesis Androstenedione - metabolism Animals Biochemistry Biological and medical sciences Brain Brain - metabolism Cell physiology Central nervous system Endocrinology Estrogens Estrogens - biosynthesis Female Fundamental and applied biological sciences. Psychology Hormonal regulation Human sexual behavior Humans Hydroxylation In Vitro Techniques Male Molecular and cellular biology Placenta Placenta - metabolism Pregnancy Rats Steroids |
| title | 19-Hydroxylation of Androgens in the Rat Brain |
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