0 11 Mononuclear mononuclear JJ 12 21 leukocyte leukocyte NN 22 36 glucocorticoid glucocorticoid NN 37 45 receptor receptor NN 46 53 binding binding NN 54 69 characteristics characteristic NNS 70 73 and and CC 74 89 down-regulation down-regulation NN 90 92 in in IN 93 98 major major JJ 99 109 depression depression NN 109 110 . . . 112 116 Some some DT 117 125 patients patient NNS 126 130 with with IN 131 136 major major JJ 137 147 depressive depressive JJ 148 156 disorder disorder NN 157 158 ( ( ( 158 161 MDD MDD NNP 161 162 ) ) ) 163 167 have have VBP 168 176 elevated elevate VBN 177 183 plasma plasma NN 184 192 cortisol cortisol NN 193 207 concentrations concentration NNS 208 211 and and CC 212 216 show show VBP 217 224 failure failure NN 225 227 to to TO 228 236 suppress suppress VB 237 245 cortisol cortisol NN 246 255 secretion secretion NN 256 260 upon upon IN 261 275 administration administration NN 276 278 of of IN 279 292 dexamethasone dexamethasone NN 293 294 ( ( ( 294 297 DEX DEX NNP 297 298 ) ) ) 298 299 , , , 300 303 yet yet RB 304 308 they they PRP 309 311 do do VBP 312 315 not not RB 316 320 have have VB 321 331 Cushingoid cushingoid JJ 332 340 features feature NNS 340 341 . . . 342 344 To to TO 345 350 study study VB 351 358 whether whether IN 359 363 this this DT 364 374 represents represent VBZ 375 389 glucocorticoid glucocorticoid NN 390 391 ( ( ( 391 393 GC GC NNP 393 394 ) ) ) 395 405 resistance resistance NN 405 406 , , , 407 408 [ [ ( 408 423 3H]-DEX-binding 3h]-dex-binding JJ 424 430 assays assay NNS 431 435 were be VBD 436 440 used use VBN 441 443 to to TO 444 451 measure measure VB 451 452 , , , 453 455 in in FW 456 461 vitro vitro FW 461 462 , , , 463 466 the the DT 467 469 GC GC NNP 470 478 receptor receptor NN 479 487 affinity affinity NN 488 489 ( ( ( 489 493 1/Kd 1/kd NN 493 494 ) ) ) 495 498 and and CC 499 505 number number NN 506 507 ( ( ( 507 511 Bmax Bmax NNP 511 512 ) ) ) 513 515 in in IN 516 527 mononuclear mononuclear JJ 528 538 leukocytes leukocyte NNS 539 541 of of IN 542 544 11 11 CD 545 548 MDD MDD NNP 549 557 patients patient NNS 558 561 and and CC 562 564 15 15 CD 565 572 control control JJ 573 581 subjects subject NNS 581 582 . . . 583 585 No no DT 586 594 receptor receptor NN 595 608 abnormalities abnormality NNS 609 613 were be VBD 614 622 detected detect VBN 623 625 in in IN 626 629 the the DT 630 633 MDD MDD NNP 634 639 group group NN 639 640 ; ; : 641 645 thus thus RB 646 649 any any DT 650 658 cellular cellular JJ 659 665 defect defect NN 666 673 leading lead VBG 674 676 to to TO 677 678 a a DT 679 683 lack lack NN 684 686 of of IN 687 701 responsiveness responsiveness NN 702 704 to to TO 705 707 GC GC NNP 708 710 in in IN 711 714 the the DT 715 718 MDD MDD NNP 719 727 patients patient NNS 727 728 , , , 729 731 if if IN 732 739 present present NN 739 740 , , , 741 749 probably probably RB 750 754 lies lie VBZ 755 761 beyond beyond IN 762 765 the the DT 766 773 initial initial JJ 774 782 receptor receptor NN 783 790 binding binding NN 790 791 . . . 792 795 DEX DEX NNP 796 797 ( ( ( 797 800 1.0 1.0 CD 801 803 mg mg NN 804 810 orally orally RB 810 811 ) ) ) 812 815 was be VBD 816 828 administered administer VBN 829 831 to to TO 832 837 study study VB 838 840 in in FW 841 845 vivo vivo FW 846 848 GC GC NNP 849 857 receptor receptor NN 858 873 down-regulation down-regulation NN 873 874 . . . 875 883 Compared compare VBN 884 886 to to TO 887 890 the the DT 891 898 control control NN 899 904 group group NN 904 905 , , , 906 911 fewer few JJR 912 921 depressed depressed JJ 922 930 subjects subject NNS 931 945 down-regulated down-regulate VBD 946 950 Bmax Bmax NNP 951 956 after after IN 957 960 DEX DEX NNP 960 961 . . . 962 964 By by IN 965 971 paired paired JJ 972 978 t-test t-test NN 978 979 , , , 980 984 Bmax Bmax NNP 985 994 decreased decrease VBD 995 1008 significantly significantly RB 1009 1011 in in IN 1012 1015 the the DT 1016 1023 control control NN 1024 1029 group group NN 1030 1033 but but CC 1034 1037 not not RB 1038 1040 in in IN 1041 1044 the the DT 1045 1054 depressed depressed JJ 1055 1060 group group NN 1060 1061 . . . 1062 1070 Receptor receptor NN 1071 1077 number number NN 1078 1080 on on IN 1081 1084 the the DT 1085 1092 control control NN 1093 1096 day day NN 1097 1100 did do VBD 1101 1104 not not RB 1105 1114 correlate correlate VB 1115 1128 significantly significantly RB 1129 1133 with with IN 1134 1137 the the DT 1138 1144 degree degree NN 1145 1147 of of IN 1148 1156 receptor receptor NN 1157 1172 down-regulation down-regulation NN 1172 1173 , , , 1174 1182 severity severity NN 1183 1185 of of IN 1186 1196 depression depression NN 1197 1199 or or CC 1200 1208 cortisol cortisol NN 1209 1223 concentrations concentration NNS 1224 1230 across across IN 1231 1234 all all PDT 1235 1238 the the DT 1239 1247 subjects subject NNS 1247 1248 . . . 1249 1254 These these DT 1255 1262 results result NNS 1263 1265 do do VBP 1266 1269 not not RB 1270 1274 lend lend VB 1275 1282 support support NN 1283 1285 to to TO 1286 1294 previous previous JJ 1295 1302 reports report NNS 1303 1313 suggesting suggest VBG 1314 1318 that that IN 1319 1321 GC GC NNP 1322 1332 resistance resistance NN 1333 1335 in in IN 1336 1339 MDD MDD NNP 1340 1347 results result VBZ 1348 1352 from from IN 1353 1354 a a DT 1355 1357 GC GC NNP 1358 1374 receptor-binding receptor-binding JJ 1375 1386 abnormality abnormality NN 1386 1387 , , , 1388 1391 and and CC 1392 1396 they they PRP 1397 1406 emphasize emphasize VBP 1407 1410 the the DT 1411 1421 importance importance NN 1422 1424 of of IN 1425 1436 considering consider VBG 1437 1445 receptor receptor NN 1446 1453 studies study NNS 1454 1456 in in IN 1457 1460 the the DT 1461 1468 context context NN 1469 1471 of of IN 1472 1483 GC-mediated gc-mediated JJ 1484 1488 cell cell NN 1489 1498 processes process NNS 1499 1501 in in IN 1502 1507 order order NN 1508 1510 to to TO 1511 1519 identify identify VB 1520 1523 the the DT 1524 1529 exact exact JJ 1530 1538 cellular cellular JJ 1539 1548 defect(s) defect(s) NN 1549 1556 leading lead VBG 1557 1559 to to TO 1560 1562 GC GC NNP 1563 1573 resistance resistance NN 1573 1574 . . .