Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole
Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐...
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| Veröffentlicht in: | Synapse (New York, N.Y.) N.Y.), 2010-11, Vol.64 (11), p.801-807 |
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| creator | Biegon, Anat Kim, Sung Won Alexoff, David L. Jayne, Millard Carter, Pauline Hubbard, Barbara King, Payton Logan, Jean Muench, Lisa Pareto, Deborah Schlyer, David Shea, Colleen Telang, Frank Wang, Gene-Jack Xu, Youwen Fowler, Joanna S. |
| description | Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (VT) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/syn.20791 |
| format | Article |
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Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (VT) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc.</description><identifier>ISSN: 0887-4476</identifier><identifier>ISSN: 1098-2396</identifier><identifier>EISSN: 1098-2396</identifier><identifier>DOI: 10.1002/syn.20791</identifier><identifier>PMID: 20842717</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aggression ; androgens ; Aromatase ; Aromatase - metabolism ; Aromatase Inhibitors - pharmacokinetics ; BIOSYNTHESIS ; BRAIN ; Brain - diagnostic imaging ; Brain - drug effects ; Brain - enzymology ; Brain Mapping ; CEREBELLUM ; Cognition ; Cortex (temporal) ; DISTRIBUTION ; estrogen ; ESTROGENS ; Female ; Humans ; imaging ; IN VIVO ; KINETICS ; Male ; Medulla oblongata ; MENSTRUAL CYCLE ; METABOLITES ; Nucleus accumbens ; PET ; PHYSICS OF ELEMENTARY PARTICLES AND FIELDS ; PLASMA ; Pons ; Positron emission tomography ; POSITRONS ; Preoptic area ; Protein Binding - drug effects ; Putamen ; RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY ; Radiopharmaceuticals - pharmacokinetics ; SPECIFICITY ; steroidogenesis ; Substantia alba ; Synapses ; testosterone ; THALAMUS ; Tissue Distribution ; TOMOGRAPHY ; Triazoles - pharmacokinetics ; Young Adult</subject><ispartof>Synapse (New York, N.Y.), 2010-11, Vol.64 (11), p.801-807</ispartof><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5121-18149592ffb017c869396373f1c82ca649a85f9e13e6ae01dabd3c0b6f0638df3</citedby><cites>FETCH-LOGICAL-c5121-18149592ffb017c869396373f1c82ca649a85f9e13e6ae01dabd3c0b6f0638df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fsyn.20791$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fsyn.20791$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20842717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1014325$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Biegon, Anat</creatorcontrib><creatorcontrib>Kim, Sung Won</creatorcontrib><creatorcontrib>Alexoff, David L.</creatorcontrib><creatorcontrib>Jayne, Millard</creatorcontrib><creatorcontrib>Carter, Pauline</creatorcontrib><creatorcontrib>Hubbard, Barbara</creatorcontrib><creatorcontrib>King, Payton</creatorcontrib><creatorcontrib>Logan, Jean</creatorcontrib><creatorcontrib>Muench, Lisa</creatorcontrib><creatorcontrib>Pareto, Deborah</creatorcontrib><creatorcontrib>Schlyer, David</creatorcontrib><creatorcontrib>Shea, Colleen</creatorcontrib><creatorcontrib>Telang, Frank</creatorcontrib><creatorcontrib>Wang, Gene-Jack</creatorcontrib><creatorcontrib>Xu, Youwen</creatorcontrib><creatorcontrib>Fowler, Joanna S.</creatorcontrib><creatorcontrib>BROOKHAVEN NATIONAL LABORATORY (BNL)</creatorcontrib><title>Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole</title><title>Synapse (New York, N.Y.)</title><addtitle>Synapse</addtitle><description>Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (VT) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc.</description><subject>Adult</subject><subject>Aggression</subject><subject>androgens</subject><subject>Aromatase</subject><subject>Aromatase - metabolism</subject><subject>Aromatase Inhibitors - pharmacokinetics</subject><subject>BIOSYNTHESIS</subject><subject>BRAIN</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain Mapping</subject><subject>CEREBELLUM</subject><subject>Cognition</subject><subject>Cortex (temporal)</subject><subject>DISTRIBUTION</subject><subject>estrogen</subject><subject>ESTROGENS</subject><subject>Female</subject><subject>Humans</subject><subject>imaging</subject><subject>IN VIVO</subject><subject>KINETICS</subject><subject>Male</subject><subject>Medulla oblongata</subject><subject>MENSTRUAL CYCLE</subject><subject>METABOLITES</subject><subject>Nucleus accumbens</subject><subject>PET</subject><subject>PHYSICS OF ELEMENTARY PARTICLES AND FIELDS</subject><subject>PLASMA</subject><subject>Pons</subject><subject>Positron emission tomography</subject><subject>POSITRONS</subject><subject>Preoptic area</subject><subject>Protein Binding - drug effects</subject><subject>Putamen</subject><subject>RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>SPECIFICITY</subject><subject>steroidogenesis</subject><subject>Substantia alba</subject><subject>Synapses</subject><subject>testosterone</subject><subject>THALAMUS</subject><subject>Tissue Distribution</subject><subject>TOMOGRAPHY</subject><subject>Triazoles - pharmacokinetics</subject><subject>Young Adult</subject><issn>0887-4476</issn><issn>1098-2396</issn><issn>1098-2396</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0EotvCgRdAFid6SOuxs07MoRJaylKpWlZqqwohZDmOQwyJXWxny_L0pKRdwYGTD_PN55n5EXoB5AgIocdx644oKQQ8QjMgoswoE_wxmpGyLLI8L_ge2o_xGyGEAcmfoj1KypwWUMxQe-Xsj8Hg2sYUbDUk6x32DVbB9yqpaLB1OLUGt0OvHK6Csu4NPnN4YzcexzTU1kR8a1OL16eXWLkaf15lvUnttssAFl82PvhfvjPP0JNGddE8v38P0NX708vFh-z84_Js8fY803OgkEEJuZgL2jQVgUKXXIyrsII1oEuqFc-FKueNMMAMV4ZAraqaaVLxhnBW1g07QCeT92aoelNr41JQnbwJtldhK72y8t-Ks6386jeSihwoI6Pg1STwMVkZtU1Gt9o7Z3SSQCBndD5Cr-9_CX48X0yyt1GbrlPO-CHecYXgFCgf0cMJ1cHHGEyzmwWIvItPjvHJP_GN7Mu_h9-RD3mNwPEE3NrObP9vkhefVg_KbOoYAzY_dx0qfJe8YMVcXq-Wcn0NYrl-dyGX7Df3KrQT</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Biegon, Anat</creator><creator>Kim, Sung Won</creator><creator>Alexoff, David L.</creator><creator>Jayne, Millard</creator><creator>Carter, Pauline</creator><creator>Hubbard, Barbara</creator><creator>King, Payton</creator><creator>Logan, Jean</creator><creator>Muench, Lisa</creator><creator>Pareto, Deborah</creator><creator>Schlyer, David</creator><creator>Shea, Colleen</creator><creator>Telang, Frank</creator><creator>Wang, Gene-Jack</creator><creator>Xu, Youwen</creator><creator>Fowler, Joanna S.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>201011</creationdate><title>Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole</title><author>Biegon, Anat ; Kim, Sung Won ; Alexoff, David L. ; Jayne, Millard ; Carter, Pauline ; Hubbard, Barbara ; King, Payton ; Logan, Jean ; Muench, Lisa ; Pareto, Deborah ; Schlyer, David ; Shea, Colleen ; Telang, Frank ; Wang, Gene-Jack ; Xu, Youwen ; Fowler, Joanna S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5121-18149592ffb017c869396373f1c82ca649a85f9e13e6ae01dabd3c0b6f0638df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aggression</topic><topic>androgens</topic><topic>Aromatase</topic><topic>Aromatase - metabolism</topic><topic>Aromatase Inhibitors - pharmacokinetics</topic><topic>BIOSYNTHESIS</topic><topic>BRAIN</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Brain Mapping</topic><topic>CEREBELLUM</topic><topic>Cognition</topic><topic>Cortex (temporal)</topic><topic>DISTRIBUTION</topic><topic>estrogen</topic><topic>ESTROGENS</topic><topic>Female</topic><topic>Humans</topic><topic>imaging</topic><topic>IN VIVO</topic><topic>KINETICS</topic><topic>Male</topic><topic>Medulla oblongata</topic><topic>MENSTRUAL CYCLE</topic><topic>METABOLITES</topic><topic>Nucleus accumbens</topic><topic>PET</topic><topic>PHYSICS OF ELEMENTARY PARTICLES AND FIELDS</topic><topic>PLASMA</topic><topic>Pons</topic><topic>Positron emission tomography</topic><topic>POSITRONS</topic><topic>Preoptic area</topic><topic>Protein Binding - drug effects</topic><topic>Putamen</topic><topic>RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>SPECIFICITY</topic><topic>steroidogenesis</topic><topic>Substantia alba</topic><topic>Synapses</topic><topic>testosterone</topic><topic>THALAMUS</topic><topic>Tissue Distribution</topic><topic>TOMOGRAPHY</topic><topic>Triazoles - pharmacokinetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biegon, Anat</creatorcontrib><creatorcontrib>Kim, Sung Won</creatorcontrib><creatorcontrib>Alexoff, David L.</creatorcontrib><creatorcontrib>Jayne, Millard</creatorcontrib><creatorcontrib>Carter, Pauline</creatorcontrib><creatorcontrib>Hubbard, Barbara</creatorcontrib><creatorcontrib>King, Payton</creatorcontrib><creatorcontrib>Logan, Jean</creatorcontrib><creatorcontrib>Muench, Lisa</creatorcontrib><creatorcontrib>Pareto, Deborah</creatorcontrib><creatorcontrib>Schlyer, David</creatorcontrib><creatorcontrib>Shea, Colleen</creatorcontrib><creatorcontrib>Telang, Frank</creatorcontrib><creatorcontrib>Wang, Gene-Jack</creatorcontrib><creatorcontrib>Xu, Youwen</creatorcontrib><creatorcontrib>Fowler, Joanna S.</creatorcontrib><creatorcontrib>BROOKHAVEN NATIONAL LABORATORY (BNL)</creatorcontrib><collection>Istex</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>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Synapse (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biegon, Anat</au><au>Kim, Sung Won</au><au>Alexoff, David L.</au><au>Jayne, Millard</au><au>Carter, Pauline</au><au>Hubbard, Barbara</au><au>King, Payton</au><au>Logan, Jean</au><au>Muench, Lisa</au><au>Pareto, Deborah</au><au>Schlyer, David</au><au>Shea, Colleen</au><au>Telang, Frank</au><au>Wang, Gene-Jack</au><au>Xu, Youwen</au><au>Fowler, Joanna S.</au><aucorp>BROOKHAVEN NATIONAL LABORATORY (BNL)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole</atitle><jtitle>Synapse (New York, N.Y.)</jtitle><addtitle>Synapse</addtitle><date>2010-11</date><risdate>2010</risdate><volume>64</volume><issue>11</issue><spage>801</spage><epage>807</epage><pages>801-807</pages><issn>0887-4476</issn><issn>1098-2396</issn><eissn>1098-2396</eissn><abstract>Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐11C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (VT) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20842717</pmid><doi>10.1002/syn.20791</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aggression androgens Aromatase Aromatase - metabolism Aromatase Inhibitors - pharmacokinetics BIOSYNTHESIS BRAIN Brain - diagnostic imaging Brain - drug effects Brain - enzymology Brain Mapping CEREBELLUM Cognition Cortex (temporal) DISTRIBUTION estrogen ESTROGENS Female Humans imaging IN VIVO KINETICS Male Medulla oblongata MENSTRUAL CYCLE METABOLITES Nucleus accumbens PET PHYSICS OF ELEMENTARY PARTICLES AND FIELDS PLASMA Pons Positron emission tomography POSITRONS Preoptic area Protein Binding - drug effects Putamen RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY Radiopharmaceuticals - pharmacokinetics SPECIFICITY steroidogenesis Substantia alba Synapses testosterone THALAMUS Tissue Distribution TOMOGRAPHY Triazoles - pharmacokinetics Young Adult |
| title | Unique distribution of aromatase in the human brain: In vivo studies with PET and [N-methyl-11C]vorozole |
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