;PMID: 12667489 ;source_file_1861.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..47] = [t:0..47] ;1)sentence:[e:53..204] = [t:53..204] ;2)section:[e:208..263] = [t:208..263] ;3)section:[e:267..370] = [t:267..370] ;4)sentence:[e:374..649] = [t:374..649] ;5)sentence:[e:650..761] = [t:650..761] ;6)sentence:[e:762..918] = [t:762..918] ;7)sentence:[e:919..1054] = [t:919..1054] ;8)sentence:[e:1056..1210] = [t:1056..1210] ;9)sentence:[e:1211..1349] = [t:1211..1349] ;10)sentence:[e:1350..1524] = [t:1350..1524] ;11)sentence:[e:1526..1693] = [t:1526..1693] ;12)sentence:[e:1694..1757] = [t:1694..1757] ;13)sentence:[e:1758..1914] = [t:1758..1914] ;14)sentence:[e:1915..2184] = [t:1915..2184] ;15)sentence:[e:2185..2335] = [t:2185..2335] ;16)section:[e:2339..2384] = [t:2339..2384] ;section 0 Span:0..47 ;Arch Biochem Biophys. 2003 Apr 15;412(2):251-8. (SEC (FRAG (NNP:[0..4] Arch) (NNP:[5..12] Biochem) (NNP:[13..20] Biophys) (.:[20..21] .) (CD:[22..26] 2003) (NNP:[27..30] Apr) (CD:[31..33] 15) (CC:[33..38] ;412-LRB-) (CD:[38..39] 2) (-RRB-:[39..40] -RRB-) (CD:[40..44] :251) (::[44..45] -) (CD:[45..47] 8.))) ;sentence 1 Span:53..204 ;Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of ; dehydroepiandrosterone: a role for 11beta-hydroxysteroid dehydrogenases? ;[53..68]:substance:"Glucocorticoids" ;[96..105]...[116..127]:substance:"7-hydroxy"..."metabolites" ;[110..127]:substance:"7-oxo metabolites" ;[132..154]:substance:"dehydroepiandrosterone" ;[167..203]:substance:"11beta-hydroxysteroid dehydrogenases" (SENT (FRAG-HLN (S (NP-SBJ (NNS:[53..68] Glucocorticoids)) (VP (VBP:[69..76] inhibit) (NP (NP (NN:[77..92] interconversion)) (PP (IN:[93..95] of) (NP (NP (NP (JJ:[96..105] 7-hydroxy) (NML-1 (-NONE-:[105..105] *P*))) (CC:[106..109] and) (NP (JJ:[110..115] 7-oxo) (NML-1 (NNS:[116..127] metabolites)))) (PP (IN:[128..130] of) (NP (NN:[132..154] dehydroepiandrosterone)))))))) (::[154..155] :) (NP (NP (DT:[156..157] a) (NN:[158..162] role)) (PP (IN:[163..166] for) (NP (NN:[167..188] 11beta-hydroxysteroid) (NNS:[189..203] dehydrogenases))) (.:[203..204] ?)))) ;section 2 Span:208..263 ;Robinzon B, Michael KK, Ripp SL, Winters SJ, Prough RA. (SEC (FRAG (NNP:[208..216] Robinzon) (NNP:[217..218] B) (,:[218..219] ,) (NNP:[220..227] Michael) (NNP:[228..230] KK) (,:[230..231] ,) (NNP:[232..236] Ripp) (NNP:[237..239] SL) (,:[239..240] ,) (NNP:[241..248] Winters) (NNP:[249..251] SJ) (,:[251..252] ,) (NNP:[253..259] Prough) (NNP:[260..263] RA.))) ;section 3 Span:267..370 ;Department of Biochemistry, University of Louisville Health Science Center, ;Louisville, KY 40292, USA. (SEC (FRAG (NNP:[267..277] Department) (IN:[278..280] of) (NNP:[281..293] Biochemistry) (,:[293..294] ,) (NNP:[295..305] University) (IN:[306..308] of) (NNP:[309..319] Louisville) (NNP:[320..326] Health) (NNP:[327..334] Science) (NNP:[335..341] Center) (,:[341..342] ,) (NNP:[344..354] Louisville) (,:[354..355] ,) (NNP:[356..358] KY) (CD:[359..364] 40292) (,:[364..365] ,) (NNP:[366..369] USA) (.:[369..370] .))) ;sentence 4 Span:374..649 ;The cytochrome p450-dependent formation and subsequent interconversion of ;dehydroepiandrosterone (DHEA) metabolites 7 alpha-hydroxy-DHEA (7 ;alpha-OH-DHEA), 7 beta-hydroxy-DHEA (7 beta-OH-DHEA), and 7-oxo-DHEA was ;observed in human, pig, and rat liver microsomal fractions. ;[378..393]:cyp450:"cytochrome p450" ;[449..490]:substance:"dehydroepiandrosterone (DHEA) metabolites" ;[491..511]:substance:"7 alpha-hydroxy-DHEA" ;[513..529]:substance:"7 alpha-OH-DHEA" ;[532..551]:substance:"7 beta-hydroxy-DHEA" ;[553..567]:substance:"7 beta-OH-DHEA" ;[574..584]:substance:"7-oxo-DHEA" (SENT (S (NP-SBJ-4 (NP (DT:[374..377] The) (NML (NML (ADJP (NML (NN:[378..388] cytochrome) (NN:[389..393] p450)) (HYPH:[393..394] -) (JJ:[394..403] dependent)) (NN:[404..413] formation)) (CC:[414..417] and) (NML (JJ:[418..428] subsequent) (NN:[429..444] interconversion)))) (PP (IN:[445..447] of) (NP (NP (NML (NML (NN:[449..471] dehydroepiandrosterone)) (NP (-LRB-:[472..473] -LRB-) (NN:[473..477] DHEA) (-RRB-:[477..478] -RRB-))) (NNS:[479..490] metabolites)) (NP (NP (NP (CD:[491..492] 7) (NN:[493..511] alpha-hydroxy-DHEA)) (NP (-LRB-:[512..513] -LRB-) (CD:[513..514] 7) (NN:[516..529] alpha-OH-DHEA) (-RRB-:[529..530] -RRB-))) (,:[530..531] ,) (NP (NP (CD:[532..533] 7) (NN:[534..551] beta-hydroxy-DHEA)) (NP (-LRB-:[552..553] -LRB-) (CD:[553..554] 7) (NN:[555..567] beta-OH-DHEA) (-RRB-:[567..568] -RRB-))) (,:[568..569] ,) (CC:[570..573] and) (NP (NN:[574..584] 7-oxo-DHEA)))))) (VP (VBD:[585..588] was) (VP (VBN:[590..598] observed) (NP-4 (-NONE-:[598..598] *)) (PP-LOC (IN:[599..601] in) (NP (NP (JJ:[602..607] human) (NML-1 (-NONE-:[607..607] *P*))) (,:[607..608] ,) (NP (NN:[609..612] pig) (NML-1 (-NONE-:[612..612] *P*))) (,:[612..613] ,) (CC:[614..617] and) (NP (NN:[618..621] rat) (NML-1 (NN:[622..627] liver) (JJ:[628..638] microsomal) (NNS:[639..648] fractions))))))) (.:[648..649] .))) ;sentence 5 Span:650..761 ;Rat liver mitochondria and nuclei also converted DHEA to 7 alpha-OH-DHEA and ;7-oxo-DHEA, but at a lower rate. ;[700..704]:substance:"DHEA" ;[708..723]:substance:"7 alpha-OH-DHEA" ;[728..738]:substance:"7-oxo-DHEA" (SENT (S (NP-SBJ (NP (NML-2 (NN:[650..653] Rat) (NN:[654..659] liver)) (NNS:[661..673] mitochondria)) (CC:[674..677] and) (NP (NML-2 (-NONE-:[677..677] *P*)) (NNS:[678..684] nuclei))) (VP (VP (ADVP (RB:[685..689] also)) (VBD:[690..699] converted) (NP (NN:[700..704] DHEA)) (PP-CLR (TO:[705..707] to) (NP (NP (CD:[708..709] 7) (NN:[710..723] alpha-OH-DHEA)) (CC:[724..727] and) (NP (NN:[728..738] 7-oxo-DHEA))))) (,:[738..739] ,) (CC:[741..744] but) (FRAG (PP-MNR (IN:[745..747] at) (NP (DT:[748..749] a) (JJR:[750..755] lower) (NN:[756..760] rate))))) (.:[760..761] .))) ;sentence 6 Span:762..918 ;With NADP(+), and less so with NAD(+), rat, pig, and human liver microsomes ;and rat liver mitochondria and nuclei converted 7 alpha-OH-DHEA to ;7-oxo-DHEA. ;[767..774]:substance:"NADP(+)" ;[793..799]:substance:"NAD(+)" ;[887..902]:substance:"7 alpha-OH-DHEA" ;[907..917]:substance:"7-oxo-DHEA" (SENT (S (PP (PP (IN:[762..766] With) (NP (NN:[767..771] NADP) (-LRB-:[771..772] -LRB-) (SYM:[772..773] +) (-RRB-:[773..774] -RRB-))) (,:[774..775] ,) (CC:[776..779] and) (PP (ADVP-EXT (RBR:[780..784] less) (RB:[785..787] so)) (IN:[788..792] with) (NP (NN:[793..796] NAD) (-LRB-:[796..797] -LRB-) (SYM:[797..798] +) (-RRB-:[798..799] -RRB-)))) (,:[799..800] ,) (NP-SBJ (NP (NP (NN:[801..804] rat) (NML-3 (-NONE-:[804..804] *P*))) (,:[804..805] ,) (NP (NN:[806..809] pig) (NML-3 (-NONE-:[809..809] *P*))) (,:[809..810] ,) (CC:[811..814] and) (NP (JJ:[815..820] human) (NML-3 (NN:[822..827] liver) (NNS:[828..838] microsomes)))) (CC:[839..842] and) (NP (NP (NML-2 (NN:[843..846] rat)) (NN:[847..852] liver) (NNS:[853..865] mitochondria)) (CC:[866..869] and) (NP (NML-2 (-NONE-:[869..869] *P*)) (NNS:[870..876] nuclei)))) (VP (VBD:[877..886] converted) (NP (CD:[887..888] 7) (NN:[889..902] alpha-OH-DHEA)) (PP-CLR (TO:[904..906] to) (NP (NN:[907..917] 7-oxo-DHEA)))) (.:[917..918] .))) ;sentence 7 Span:919..1054 ;This reaction was inhibited by corticosterone and the 11 beta-hydroxysteroid ;dehydrogenase (11 betaHSD) inhibitor carbenoxolone (CBX). ;[950..964]:substance:"corticosterone" ;[973..1010]:substance:"11 beta-hydroxysteroid dehydrogenase" ;[1012..1022]:substance:"11 betaHSD" ;[1024..1033]:substance:"inhibitor" ;[1034..1047]:substance:"carbenoxolone" ;[1049..1052]:substance:"CBX" (SENT (S (NP-SBJ-1 (DT:[919..923] This) (NN:[924..932] reaction)) (VP (VBD:[933..936] was) (VP (VBN:[937..946] inhibited) (NP-1 (-NONE-:[946..946] *)) (PP (IN:[947..949] by) (NP-LGS (NP (NN:[950..964] corticosterone)) (CC:[965..968] and) (NP (NP (DT:[969..972] the) (NML (NML (CD:[973..975] 11) (NN:[977..996] beta-hydroxysteroid) (NN:[997..1010] dehydrogenase)) (NML (-LRB-:[1011..1012] -LRB-) (CD:[1012..1014] 11) (NN:[1015..1022] betaHSD) (-RRB-:[1022..1023] -RRB-))) (NN:[1024..1033] inhibitor)) (NP (NP (NN:[1034..1047] carbenoxolone)) (NP (-LRB-:[1048..1049] -LRB-) (NN:[1049..1052] CBX) (-RRB-:[1052..1053] -RRB-)))))))) (.:[1053..1054] .))) ;sentence 8 Span:1056..1210 ;The conversion of 7 alpha-OH-DHEA to 7-oxo-DHEA by rat kidney occurred at ;higher rates with NAD(+) than with NADP(+) and was inhibited by ;corticosterone. ;[1074..1089]:substance:"7 alpha-OH-DHEA" ;[1093..1103]:substance:"7-oxo-DHEA" ;[1149..1155]:substance:"NAD(+)" ;[1166..1173]:substance:"NADP(+)" ;[1195..1209]:substance:"corticosterone" (SENT (S (NP-SBJ-1 (NP (DT:[1056..1059] The) (NN:[1060..1070] conversion)) (PP (IN:[1071..1073] of) (NP (CD:[1074..1075] 7) (NN:[1076..1089] alpha-OH-DHEA))) (PP (TO:[1090..1092] to) (NP (NN:[1093..1103] 7-oxo-DHEA))) (PP (IN:[1104..1106] by) (NP (NN:[1107..1110] rat) (NN:[1111..1117] kidney)))) (VP (VP (VBD:[1118..1126] occurred) (PP (IN:[1127..1129] at) (NP (JJR:[1130..1136] higher) (NNS:[1138..1143] rates))) (PP (IN:[1144..1148] with) (NP (NN:[1149..1152] NAD) (-LRB-:[1152..1153] -LRB-) (SYM:[1153..1154] +) (-RRB-:[1154..1155] -RRB-))) (PP (IN:[1156..1160] than) (PP (IN:[1161..1165] with) (NP (NN:[1166..1170] NADP) (-LRB-:[1170..1171] -LRB-) (SYM:[1171..1172] +) (-RRB-:[1172..1173] -RRB-))))) (CC:[1174..1177] and) (VP (VBD:[1178..1181] was) (VP (VBN:[1182..1191] inhibited) (NP-1 (-NONE-:[1191..1191] *)) (PP (IN:[1192..1194] by) (NP-LGS (NN:[1195..1209] corticosterone)))))) (.:[1209..1210] .))) ;sentence 9 Span:1211..1349 ;With NADPH, 7-oxo-DHEA was converted to unidentified hydroxylated ;metabolites and low levels of 7 alpha-OH-DHEA by rat liver microsomes. ;[1217..1222]:substance:"NADPH" ;[1224..1234]:substance:"7-oxo-DHEA" ;[1278..1289]:substance:"metabolites" ;[1309..1324]:substance:"7 alpha-OH-DHEA" (SENT (S (PP (IN:[1211..1215] With) (NP (NN:[1217..1222] NADPH))) (,:[1222..1223] ,) (NP-SBJ-1 (NN:[1224..1234] 7-oxo-DHEA)) (VP (VBD:[1235..1238] was) (VP (VBN:[1239..1248] converted) (NP-1 (-NONE-:[1248..1248] *)) (PP-CLR (TO:[1249..1251] to) (NP (NP (JJ:[1252..1264] unidentified) (VBN:[1265..1277] hydroxylated) (NNS:[1278..1289] metabolites)) (CC:[1290..1293] and) (NP (NP (JJ:[1294..1297] low) (NNS:[1299..1305] levels)) (PP (IN:[1306..1308] of) (NP (CD:[1309..1310] 7) (NN:[1311..1324] alpha-OH-DHEA)))))) (PP (IN:[1325..1327] by) (NP-LGS (NN:[1328..1331] rat) (NN:[1332..1337] liver) (NNS:[1338..1348] microsomes))))) (.:[1348..1349] .))) ;sentence 10 Span:1350..1524 ;In contrast, pig liver microsomal fractions reduced 7-oxo-DHEA to nearly ;equal amounts of 7 alpha- and 7 beta-OH-DHEA, while human fractions produced ;mainly 7 beta-OH-DHEA. ;[1403..1413]:substance:"7-oxo-DHEA" ;[1441..1449]...[1462..1469]:substance:"7 alpha-"..."OH-DHEA" ;[1455..1469]:substance:"7 beta-OH-DHEA" ;[1509..1523]:substance:"7 beta-OH-DHEA" (SENT (S (PP (IN:[1350..1352] In) (NP (NN:[1353..1361] contrast))) (,:[1361..1362] ,) (NP-SBJ (NN:[1363..1366] pig) (NN:[1367..1372] liver) (JJ:[1374..1384] microsomal) (NNS:[1385..1394] fractions)) (VP (VBD:[1395..1402] reduced) (NP (NN:[1403..1413] 7-oxo-DHEA)) (PP-CLR (TO:[1414..1416] to) (NP (NP (ADJP (RB:[1417..1423] nearly) (JJ:[1424..1429] equal)) (NNS:[1430..1437] amounts)) (PP (IN:[1438..1440] of) (NP (NP (CD:[1441..1442] 7) (SYM:[1443..1448] alpha) (HYPH:[1448..1449] -) (NML-1 (-NONE-:[1449..1449] *P*))) (CC:[1450..1453] and) (NP (CD:[1455..1456] 7) (SYM:[1457..1461] beta) (HYPH:[1461..1462] -) (NML-1 (NN:[1462..1469] OH-DHEA))))))) (,:[1469..1470] ,) (SBAR-ADV (IN:[1471..1476] while) (S (NP-SBJ (JJ:[1477..1482] human) (NNS:[1483..1492] fractions)) (VP (VBD:[1493..1501] produced) (ADVP (RB:[1502..1508] mainly)) (NP (CD:[1509..1510] 7) (NN:[1511..1523] beta-OH-DHEA)))))) (.:[1523..1524] .))) ;sentence 11 Span:1526..1693 ;Dehydrocorticosterone inhibited the reduction to both isomers by pig liver ;microsomes, but only to 7 alpha-OH-DHEA by human microsomes; CBX inhibited ;both reactions. ;[1526..1547]:substance:"Dehydrocorticosterone" ;[1580..1587]:substance:"isomers" ;[1626..1641]:substance:"7 alpha-OH-DHEA" ;[1663..1666]:substance:"CBX" (SENT (S (S (NP-SBJ (NN:[1526..1547] Dehydrocorticosterone)) (VP (VP (VBD:[1548..1557] inhibited) (NP (NP (DT:[1558..1561] the) (NN:[1562..1571] reduction)) (PP=2 (TO:[1572..1574] to) (NP (DT:[1575..1579] both) (NNS:[1580..1587] isomers))) (PP=3 (IN:[1588..1590] by) (NP (NN:[1591..1594] pig) (NN:[1595..1600] liver) (NNS:[1602..1612] microsomes))))) (,:[1612..1613] ,) (CC:[1614..1617] but) (VP (ADVP (RB:[1618..1622] only)) (NP (PP=2 (TO:[1623..1625] to) (NP (CD:[1626..1627] 7) (NN:[1628..1641] alpha-OH-DHEA))) (PP=3 (IN:[1642..1644] by) (NP (JJ:[1645..1650] human) (NNS:[1651..1661] microsomes))))))) (::[1661..1662] ;) (S (NP-SBJ (NN:[1663..1666] CBX)) (VP (VBD:[1667..1676] inhibited) (NP (DT:[1677..1681] both) (NNS:[1683..1692] reactions)))) (.:[1692..1693] .))) ;sentence 12 Span:1694..1757 ;Rat kidney did not reduce 7-oxo-DHEA with either NADPH or NADH. ;[1720..1730]:substance:"7-oxo-DHEA" ;[1743..1748]:substance:"NADPH" ;[1752..1756]:substance:"NADH" (SENT (S (NP-SBJ (NN:[1694..1697] Rat) (NN:[1698..1704] kidney)) (VP (VBD:[1705..1708] did) (RB:[1709..1712] not) (VP (VB:[1713..1719] reduce) (NP (NN:[1720..1730] 7-oxo-DHEA)) (PP (IN:[1731..1735] with) (NP (CC:[1736..1742] either) (NN:[1743..1748] NADPH) (CC:[1749..1751] or) (NN:[1752..1756] NADH))))) (.:[1756..1757] .))) ;sentence 13 Span:1758..1914 ;These results demonstrate that DHEA is first converted in liver to 7 ;alpha-OH-DHEA, which is subsequently oxidized to 7-oxo-DHEA in both liver ;and kidney. ;[1790..1794]:substance:"DHEA" ;[1826..1841]:substance:"7 alpha-OH-DHEA" ;[1878..1888]:substance:"7-oxo-DHEA" (SENT (S (NP-SBJ (DT:[1758..1763] These) (NNS:[1765..1772] results)) (VP (VBP:[1773..1784] demonstrate) (SBAR (IN:[1785..1789] that) (S (NP-SBJ (NN:[1790..1794] DHEA)) (VP (VBZ:[1795..1797] is) (ADVP-TMP (RB:[1798..1803] first)) (VP (VBN:[1804..1813] converted) (PP-LOC (IN:[1814..1816] in) (NP (NN:[1817..1822] liver))) (PP-CLR (TO:[1823..1825] to) (NP (NP (CD:[1826..1827] 7) (NN:[1828..1841] alpha-OH-DHEA)) (,:[1841..1842] ,) (SBAR (WHNP-1 (WDT:[1844..1849] which)) (S (NP-SBJ-1 (-NONE-:[1849..1849] *T*)) (VP (VBZ:[1850..1852] is) (ADVP-TMP (RB:[1853..1865] subsequently)) (VP (VBN:[1866..1874] oxidized) (PP-CLR (TO:[1875..1877] to) (NP (NN:[1878..1888] 7-oxo-DHEA))) (PP-LOC (IN:[1889..1891] in) (NP (CC:[1892..1896] both) (NN:[1897..1902] liver) (CC:[1903..1906] and) (NN:[1907..1913] kidney)))))))))))))) (.:[1913..1914] .))) ;sentence 14 Span:1915..2184 ;In liver, interconversion of 7-oxo-DHEA and 7-OH-DHEA isomers is largely ;catalyzed by 11 betaHSD1, while in kidney 11 betaHSD2 (NAD(+)-dependent) and ;11 betaHSD3 (NADP(+)-dependent) likely catalyze the unidirectional oxidation ;of 7 alpha-hydroxy-DHEA to 7-oxo-DHEA. ;[1945..1955]...[1970..1977]:substance:"7-oxo-DHEA"..."isomers" ;[1960..1977]:substance:"7-OH-DHEA isomers" ;[2002..2014]:substance:"11 betaHSD1" ;[2032..2043]:substance:"11 betaHSD2" ;[2045..2051]:substance:"NAD(+)" ;[2067..2078]:substance:"11 betaHSD3" ;[2081..2088]:substance:"NADP(+)" ;[2148..2169]:substance:"7 alpha-hydroxy-DHEA" ;[2173..2183]:substance:"7-oxo-DHEA" (SENT (S (PP-LOC (IN:[1915..1917] In) (NP (NN:[1918..1923] liver))) (,:[1923..1924] ,) (NP-SBJ-2 (NP (NN:[1926..1941] interconversion)) (PP (IN:[1942..1944] of) (NP (NP (NN:[1945..1955] 7-oxo-DHEA) (NML-1 (-NONE-:[1955..1955] *P*))) (CC:[1956..1959] and) (NP (NN:[1960..1969] 7-OH-DHEA) (NML-1 (NNS:[1970..1977] isomers)))))) (VP (VBZ:[1978..1980] is) (ADVP (RB:[1981..1988] largely)) (VP (VBN:[1989..1998] catalyzed) (NP-2 (-NONE-:[1998..1998] *)) (PP (IN:[1999..2001] by) (NP-LGS (CD:[2002..2004] 11) (NN:[2006..2014] betaHSD1))) (,:[2014..2015] ,) (SBAR-ADV (IN:[2016..2021] while) (S (PP-LOC (IN:[2022..2024] in) (NP (NN:[2025..2031] kidney))) (NP-SBJ (NP (CD:[2032..2034] 11) (NN:[2035..2043] betaHSD2) (PRN (-LRB-:[2044..2045] -LRB-) (ADJP (NML (NN:[2045..2048] NAD) (-LRB-:[2048..2049] -LRB-) (SYM:[2049..2050] +) (-RRB-:[2050..2051] -RRB-)) (HYPH:[2051..2052] -) (JJ:[2052..2061] dependent)) (-RRB-:[2061..2062] -RRB-))) (CC:[2063..2066] and) (NP (CD:[2067..2069] 11) (NN:[2070..2078] betaHSD3) (PRN (-LRB-:[2080..2081] -LRB-) (NML (NN:[2081..2085] NADP) (-LRB-:[2085..2086] -LRB-) (SYM:[2086..2087] +) (-RRB-:[2087..2088] -RRB-)) (HYPH:[2088..2089] -) (JJ:[2089..2098] dependent) (-RRB-:[2098..2099] -RRB-)))) (ADVP (RB:[2100..2106] likely)) (VP (VBP:[2107..2115] catalyze) (NP (NP (DT:[2116..2119] the) (JJ:[2120..2134] unidirectional) (NN:[2135..2144] oxidation)) (PP (IN:[2145..2147] of) (NP (CD:[2148..2149] 7) (NN:[2151..2169] alpha-hydroxy-DHEA))) (PP (TO:[2170..2172] to) (NP (NN:[2173..2183] 7-oxo-DHEA))))))))) (.:[2183..2184] .))) ;sentence 15 Span:2185..2335 ;Distinct species-specific routes of metabolism of DHEA and the ;interconversion of its metabolites obviate extrapolation of animal studies ;to humans. ;[2236..2240]:substance:"DHEA" ;[2272..2283]:substance:"metabolites" (SENT (S (NP-SBJ (NP (NP (JJ:[2185..2193] Distinct) (ADJP (NN:[2194..2201] species) (HYPH:[2201..2202] -) (JJ:[2202..2210] specific)) (NNS:[2211..2217] routes)) (PP (IN:[2218..2220] of) (NP (NP (NN:[2221..2231] metabolism)) (PP (IN:[2233..2235] of) (NP (NN:[2236..2240] DHEA)))))) (CC:[2241..2244] and) (NP (NP (DT:[2245..2248] the) (NN:[2249..2264] interconversion)) (PP (IN:[2265..2267] of) (NP (PRP$:[2268..2271] its) (NNS:[2272..2283] metabolites))))) (VP (VBP:[2284..2291] obviate) (NP (NP (NN:[2292..2305] extrapolation)) (PP (IN:[2306..2308] of) (NP (NN:[2310..2316] animal) (NNS:[2317..2324] studies))) (PP (TO:[2325..2327] to) (NP (NNS:[2328..2334] humans))))) (.:[2334..2335] .))) ;section 16 Span:2339..2384 ;PMID: 12667489 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2339..2343] PMID) (::[2343..2344] :) (CD:[2345..2353] 12667489) (NN:[2354..2355] -LSB-) (NNP:[2355..2361] PubMed) (::[2362..2363] -) (NN:[2364..2371] indexed) (IN:[2372..2375] for) (NNP:[2376..2384] MEDLINE-RSB-)))