The effect of aromatase inhibition on the sexual differentiation of the sheep brain
This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is...
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| Veröffentlicht in: | Endocrine 2006-06, Vol.29 (3), p.501-512 |
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| creator | Roselli, C E Schrunk, J M Stadelman, H L Resko, J A Stormshak, F |
| description | This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development. |
| doi_str_mv | 10.1385/ENDO:29:3:501 |
| format | Article |
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Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.</description><identifier>ISSN: 1355-008X</identifier><identifier>ISSN: 0969-711X</identifier><identifier>EISSN: 0969-711X</identifier><identifier>EISSN: 1559-0100</identifier><identifier>DOI: 10.1385/ENDO:29:3:501</identifier><identifier>PMID: 16943590</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>17β-Estradiol ; Androstatrienes - pharmacology ; Animals ; Animals, Newborn - blood ; Animals, Newborn - growth & development ; Aromatase ; Aromatase Inhibitors - pharmacology ; Behavior ; Behavior, Animal ; Brain - drug effects ; Brain - embryology ; Embryos ; Endocrinology ; Female ; Fertility - drug effects ; Fetuses ; Growth rate ; Intrauterine exposure ; Luteinizing hormone ; Luteinizing Hormone - metabolism ; Male ; Males ; Maternal-Fetal Exchange - drug effects ; Mounting behavior ; Pregnancy ; Pregnancy, Animal - blood ; Prenatal experience ; Puberty ; Sex differentiation ; Sex Differentiation - drug effects ; Sexual behavior ; Sexual dimorphism ; Sexual Maturation ; Sheep ; Steroids - blood ; Testosterone ; Testosterone - blood</subject><ispartof>Endocrine, 2006-06, Vol.29 (3), p.501-512</ispartof><rights>Humana Press Inc. 2006.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-3352846ab70f708518d9c7068c50be16c8b84645b0ab085b36c8229a66662f9b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16943590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Roselli, C E</creatorcontrib><creatorcontrib>Schrunk, J M</creatorcontrib><creatorcontrib>Stadelman, H L</creatorcontrib><creatorcontrib>Resko, J A</creatorcontrib><creatorcontrib>Stormshak, F</creatorcontrib><title>The effect of aromatase inhibition on the sexual differentiation of the sheep brain</title><title>Endocrine</title><addtitle>Endocrine</addtitle><description>This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.</description><subject>17β-Estradiol</subject><subject>Androstatrienes - pharmacology</subject><subject>Animals</subject><subject>Animals, Newborn - blood</subject><subject>Animals, Newborn - growth & development</subject><subject>Aromatase</subject><subject>Aromatase Inhibitors - pharmacology</subject><subject>Behavior</subject><subject>Behavior, Animal</subject><subject>Brain - drug effects</subject><subject>Brain - embryology</subject><subject>Embryos</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Fertility - drug effects</subject><subject>Fetuses</subject><subject>Growth rate</subject><subject>Intrauterine exposure</subject><subject>Luteinizing hormone</subject><subject>Luteinizing Hormone - metabolism</subject><subject>Male</subject><subject>Males</subject><subject>Maternal-Fetal Exchange - drug effects</subject><subject>Mounting behavior</subject><subject>Pregnancy</subject><subject>Pregnancy, Animal - blood</subject><subject>Prenatal experience</subject><subject>Puberty</subject><subject>Sex differentiation</subject><subject>Sex Differentiation - drug effects</subject><subject>Sexual behavior</subject><subject>Sexual dimorphism</subject><subject>Sexual Maturation</subject><subject>Sheep</subject><subject>Steroids - blood</subject><subject>Testosterone</subject><subject>Testosterone - blood</subject><issn>1355-008X</issn><issn>0969-711X</issn><issn>0969-711X</issn><issn>1559-0100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LAzEQhoMotlaPXmXB8-ok2WST3qTWDyj2YIXeQrKb0JR2tya7oP_elC04DAzM8zADL0K3GB4wFexx_vG8nBI5pVMG-AyNQXKZlxivz9EYU8ZyALEeoasYtwCEEF5eohHmsqBMwhh9rjY2s87Zqstal-nQ7nWno818s_HGd75tstRdsqL96fUuq32yg206rwfqBrqx9pCZoH1zjS6c3kV7c5oT9PUyX83e8sXy9X32tMgrimWXU8qIKLg2JbgSBMOillUJXFQMjMW8EibhghnQJmFD04YQqXkq4qShE3Q_3D2E9ru3sVPbtg9NeqkI54VgQEWRrHywqtDGGKxTh-D3OvwqDOoYoTpGqIhUVKUIk393utqbva3_7VNm9A9vvWsk</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Roselli, C E</creator><creator>Schrunk, J M</creator><creator>Stadelman, H L</creator><creator>Resko, J A</creator><creator>Stormshak, F</creator><general>Springer Nature 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></search><sort><creationdate>20060601</creationdate><title>The effect of aromatase inhibition on the sexual differentiation of the sheep brain</title><author>Roselli, C E ; Schrunk, J M ; Stadelman, H L ; Resko, J A ; Stormshak, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-3352846ab70f708518d9c7068c50be16c8b84645b0ab085b36c8229a66662f9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>17β-Estradiol</topic><topic>Androstatrienes - pharmacology</topic><topic>Animals</topic><topic>Animals, Newborn - blood</topic><topic>Animals, Newborn - growth & development</topic><topic>Aromatase</topic><topic>Aromatase Inhibitors - pharmacology</topic><topic>Behavior</topic><topic>Behavior, Animal</topic><topic>Brain - drug effects</topic><topic>Brain - embryology</topic><topic>Embryos</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Fertility - drug effects</topic><topic>Fetuses</topic><topic>Growth rate</topic><topic>Intrauterine exposure</topic><topic>Luteinizing hormone</topic><topic>Luteinizing Hormone - metabolism</topic><topic>Male</topic><topic>Males</topic><topic>Maternal-Fetal Exchange - drug effects</topic><topic>Mounting behavior</topic><topic>Pregnancy</topic><topic>Pregnancy, Animal - blood</topic><topic>Prenatal experience</topic><topic>Puberty</topic><topic>Sex differentiation</topic><topic>Sex Differentiation - drug effects</topic><topic>Sexual behavior</topic><topic>Sexual dimorphism</topic><topic>Sexual Maturation</topic><topic>Sheep</topic><topic>Steroids - blood</topic><topic>Testosterone</topic><topic>Testosterone - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roselli, C E</creatorcontrib><creatorcontrib>Schrunk, J M</creatorcontrib><creatorcontrib>Stadelman, H L</creatorcontrib><creatorcontrib>Resko, J A</creatorcontrib><creatorcontrib>Stormshak, F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Endocrine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roselli, C E</au><au>Schrunk, J M</au><au>Stadelman, H L</au><au>Resko, J A</au><au>Stormshak, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of aromatase inhibition on the sexual differentiation of the sheep brain</atitle><jtitle>Endocrine</jtitle><addtitle>Endocrine</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>29</volume><issue>3</issue><spage>501</spage><epage>512</epage><pages>501-512</pages><issn>1355-008X</issn><issn>0969-711X</issn><eissn>0969-711X</eissn><eissn>1559-0100</eissn><abstract>This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>16943590</pmid><doi>10.1385/ENDO:29:3:501</doi><tpages>12</tpages></addata></record> |
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| subjects | 17β-Estradiol Androstatrienes - pharmacology Animals Animals, Newborn - blood Animals, Newborn - growth & development Aromatase Aromatase Inhibitors - pharmacology Behavior Behavior, Animal Brain - drug effects Brain - embryology Embryos Endocrinology Female Fertility - drug effects Fetuses Growth rate Intrauterine exposure Luteinizing hormone Luteinizing Hormone - metabolism Male Males Maternal-Fetal Exchange - drug effects Mounting behavior Pregnancy Pregnancy, Animal - blood Prenatal experience Puberty Sex differentiation Sex Differentiation - drug effects Sexual behavior Sexual dimorphism Sexual Maturation Sheep Steroids - blood Testosterone Testosterone - blood |
| title | The effect of aromatase inhibition on the sexual differentiation of the sheep brain |
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