0 7 Binding binding NN 8 23 characteristics characteristic NNS 24 26 of of IN 27 30 the the DT 31 45 glucocorticoid glucocorticoid NN 46 54 receptor receptor NN 55 57 in in IN 58 68 peripheral peripheral JJ 69 74 blood blood NN 75 86 lymphocytes lymphocyte NNS 87 89 in in IN 90 98 multiple multiple JJ 99 108 sclerosis sclerosis NN 108 109 . . . 111 119 Although although IN 120 123 the the DT 124 129 exact exact JJ 130 138 etiology etiology NN 139 141 of of IN 142 150 multiple multiple JJ 151 160 sclerosis sclerosis NN 161 162 ( ( ( 162 164 MS MS NNP 164 165 ) ) ) 166 173 remains remain VBZ 174 184 unresolved unresolved JJ 184 185 , , , 186 192 immune immune JJ 193 202 reactions reaction NNS 203 206 are be VBP 207 215 believed believe VBN 216 218 to to TO 219 221 be be VB 222 225 the the DT 226 233 central central JJ 234 244 pathogenic pathogenic JJ 245 255 mechanisms mechanism NNS 255 256 . . . 257 267 Endogenous endogenous JJ 268 271 and and CC 272 283 therapeutic therapeutic JJ 284 291 steroid steroid NN 292 300 hormones hormone NNS 301 307 affect affect VBP 308 311 the the DT 312 318 immune immune JJ 319 325 system system NN 325 326 , , , 327 330 and and CC 331 343 inflammatory inflammatory JJ 344 352 diseases disease NNS 353 356 are be VBP 357 367 associated associate VBN 368 372 with with IN 373 383 activation activation NN 384 386 of of IN 387 390 the the DT 391 421 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 422 426 axis axis NN 426 427 , , , 428 437 providing provide VBG 438 446 evidence evidence NN 447 449 of of IN 450 452 an an DT 453 469 immune-endocrine immune-endocrine JJ 470 479 interplay interplay NN 479 480 . . . 481 489 Function function NN 490 495 tests test NNS 496 498 in in IN 499 501 MS ms NN 502 506 have have VBP 507 515 revealed reveal VBN 516 529 dysregulation dysregulation NN 530 532 of of IN 533 536 the the DT 537 567 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 568 574 system system NN 575 577 in in IN 578 579 a a DT 580 591 substantial substantial JJ 592 602 proportion proportion NN 603 605 of of IN 606 614 patients patient NNS 614 615 . . . 616 618 We we PRP 619 632 characterized characterize VBD 633 647 glucocorticoid glucocorticoid NN 648 656 receptor receptor NN 657 658 ( ( ( 658 660 GR GR NNP 660 661 ) ) ) 662 669 binding binding NN 670 672 in in IN 673 683 peripheral peripheral JJ 684 689 blood blood NN 690 701 lymphocytes lymphocyte NNS 702 706 from from IN 707 709 39 39 CD 710 712 MS MS NNP 713 721 patients patient NNS 722 725 and and CC 726 728 14 14 CD 729 733 age- age- NN 734 737 and and CC 738 749 sex-matched sex-matched JJ 750 758 controls control NNS 759 763 with with IN 764 771 respect respect NN 772 774 to to TO 775 787 dissociation dissociation NN 788 796 constant constant NN 797 800 and and CC 801 808 binding binding NN 809 817 capacity capacity NN 817 818 , , , 819 824 using use VBG 825 826 a a DT 827 837 whole-cell whole-cell JJ 838 845 binding binding NN 846 851 assay assay NN 852 856 with with IN 857 858 [ [ ( 858 874 3H]dexamethasone 3H]dexamethasone NNP 875 877 as as IN 878 881 the the DT 882 888 ligand ligand NN 888 889 . . . 890 892 GR GR NNP 893 900 binding binding NN 901 911 parameters parameter NNS 912 915 did do VBD 916 919 not not RB 920 926 differ differ VB 927 940 significantly significantly RB 941 948 between between IN 949 957 patients patient NNS 958 959 ( ( ( 959 961 Kd Kd NNP 962 966 8.98 8.98 CD 967 970 +/- +/- SYM 971 975 1.07 1.07 CD 976 978 nM nM NNP 978 979 , , , 980 984 Bmax Bmax NNP 985 988 183 183 CD 989 992 +/- +/- SYM 993 997 29.8 29.8 CD 998 1005 fmol/mg fmol/mg NN 1005 1006 ) ) ) 1007 1010 and and CC 1011 1019 controls control NNS 1020 1021 ( ( ( 1021 1023 Kd Kd NNP 1024 1028 9.36 9.36 CD 1029 1032 +/- +/- CC 1033 1037 1.17 1.17 CD 1038 1040 nM nM NNP 1040 1041 , , , 1042 1046 Bmax Bmax NNP 1047 1050 158 158 CD 1051 1054 +/- +/- CC 1055 1057 16 16 CD 1058 1065 fmol/mg fmol/mg NN 1065 1066 ) ) ) 1066 1067 . . . 1068 1070 No no DT 1071 1077 effect effect NN 1078 1080 of of IN 1081 1084 age age NN 1084 1085 , , , 1086 1089 sex sex NN 1089 1090 , , , 1091 1097 course course NN 1097 1098 , , , 1099 1107 duration duration NN 1108 1110 or or CC 1111 1119 severity severity NN 1120 1122 of of IN 1123 1130 disease disease NN 1130 1131 , , , 1132 1134 or or CC 1135 1140 prior prior JJ 1141 1148 steroid steroid NN 1149 1159 treatments treatment NNS 1160 1163 was be VBD 1164 1172 detected detect VBN 1172 1173 . . . 1174 1176 GR GR NNP 1177 1184 binding binding NN 1185 1195 parameters parameter NNS 1196 1200 were be VBD 1201 1209 analyzed analyze VBN 1210 1212 in in IN 1213 1221 relation relation NN 1222 1224 to to TO 1225 1228 the the DT 1229 1236 results result NNS 1237 1239 of of IN 1240 1243 the the DT 1244 1252 combined combined JJ 1253 1270 dexamethasone-CRH dexamethasone-crh NN 1271 1275 test test NN 1275 1276 , , , 1277 1282 which which WDT 1283 1291 reflects reflect VBZ 1292 1306 corticosteroid corticosteroid NN 1307 1315 receptor receptor NN 1316 1324 function function NN 1325 1327 at at IN 1328 1331 the the DT 1332 1344 hypothalamus hypothalamus NN 1344 1345 , , , 1346 1348 in in IN 1349 1351 30 30 CD 1352 1360 patients patient NNS 1361 1364 and and CC 1365 1366 9 9 CD 1367 1375 controls control NNS 1375 1376 . . . 1377 1382 While while IN 1383 1391 controls control NNS 1392 1398 showed show VBD 1399 1400 a a DT 1401 1409 moderate moderate JJ 1410 1421 correlation correlation NN 1422 1429 between between IN 1430 1437 binding binding NN 1438 1446 affinity affinity NN 1447 1449 of of IN 1450 1453 the the DT 1454 1456 GR gr NN 1457 1459 in in IN 1460 1471 lymphocytes lymphocyte NNS 1472 1475 and and CC 1476 1486 regulatory regulatory JJ 1487 1495 function function NN 1496 1498 at at IN 1499 1502 the the DT 1503 1515 hypothalamic hypothalamic JJ 1516 1521 level level NN 1521 1522 , , , 1523 1526 the the DT 1527 1535 patients patient NNS 1536 1539 did do VBD 1540 1543 not not RB 1543 1544 . . . 1545 1550 These these DT 1551 1555 data datum NNS 1556 1563 suggest suggest VBP 1564 1568 that that IN 1569 1572 the the DT 1573 1586 physiological physiological JJ 1587 1599 relationship relationship NN 1600 1607 between between IN 1608 1615 binding binding NN 1616 1619 and and CC 1620 1628 function function NN 1629 1631 of of IN 1632 1635 the the DT 1636 1650 glucocorticoid glucocorticoid NN 1651 1659 receptor receptor NN 1660 1662 is be VBZ 1663 1672 disturbed disturb VBN 1673 1675 in in IN 1676 1678 MS MS NNP 1678 1679 . . .