0 12 Nonpituitary nonpituitary JJ 13 18 human human JJ 19 28 prolactin prolactin NN 29 33 gene gene NN 34 47 transcription transcription NN 48 50 is be VBZ 51 62 independent independent JJ 63 65 of of IN 66 71 Pit-1 pit-1 NN 72 75 and and CC 76 90 differentially differentially RB 91 101 controlled control VBN 102 104 in in IN 105 116 lymphocytes lymphocyte NNS 117 120 and and CC 121 123 in in IN 124 135 endometrial endometrial JJ 136 142 stroma stroma NN 142 143 . . . 145 155 Expression expression NN 156 158 of of IN 159 162 the the DT 163 168 human human JJ 169 172 PRL PRL NNP 173 174 ( ( ( 174 178 hPRL hprl NN 178 179 ) ) ) 180 184 gene gene NN 185 187 in in IN 188 202 extrapituitary extrapituitary JJ 203 208 sites site NNS 209 213 such such JJ 214 216 as as IN 217 220 the the DT 221 227 uterus uterus NN 228 229 ( ( ( 229 241 decidualized decidualize VBN 242 253 endometrial endometrial JJ 254 260 stroma stroma NN 261 264 and and CC 265 275 myometrium myometrium NN 275 276 ) ) ) 277 280 and and CC 281 286 cells cell NNS 287 289 of of IN 290 293 the the DT 294 307 hematopoietic hematopoietic JJ 308 315 lineage lineage NN 316 318 is be VBZ 319 327 directed direct VBN 328 330 by by IN 331 333 an an DT 334 345 alternative alternative JJ 346 354 promoter promoter NN 355 360 which which WDT 361 363 is be VBZ 364 371 located located JJ 372 385 approximately approximately RB 386 387 6 6 CD 388 397 kilobases kilobas NNS 398 399 ( ( ( 399 401 kb kb NN 401 402 ) ) ) 403 411 upstream upstream RB 412 414 of of IN 415 418 the the DT 419 437 pituitary-specific pituitary-specific JJ 438 443 start start NN 444 448 site site NN 448 449 . . . 450 452 In in IN 453 458 order order NN 459 461 to to TO 462 471 delineate delineate VB 472 475 the the DT 476 491 tissue-specific tissue-specific JJ 492 502 mechanisms mechanism NNS 503 512 governing govern VBG 513 516 the the DT 517 524 control control NN 525 527 of of IN 528 540 nonpituitary nonpituitary JJ 541 544 PRL PRL NNP 545 549 gene gene NN 550 560 expression expression NN 560 561 , , , 562 564 we we PRP 565 569 have have VBP 570 576 cloned clone VBN 577 580 and and CC 581 590 sequenced sequence VBN 591 592 3 3 CD 593 595 kb kb NN 596 607 5’-flanking 5'-flanking JJ 608 611 DNA dna NN 612 614 of of IN 615 618 the the DT 619 627 upstream upstream JJ 628 645 decidual/lymphoid decidual/lymphoid JJ 646 647 ( ( ( 647 651 dPRL dprl NN 651 652 ) ) ) 653 661 promoter promoter NN 661 662 . . . 663 668 Based base VBN 669 671 on on IN 672 680 sequence sequence NN 681 689 homology homology NN 690 692 we we PRP 693 703 identified identify VBD 704 707 two two CD 708 715 binding bind VBG 716 722 motifs motif NNS 723 726 for for IN 727 732 Pit-1 pit-1 NN 733 736 and and CC 737 742 seven seven CD 743 753 half-sites half-site NNS 754 757 for for IN 758 772 glucocorticoid glucocorticoid NN 773 794 receptor/progesterone receptor/progesterone NN 795 803 receptor receptor NN 804 805 ( ( ( 805 807 PR PR NNP 807 808 ) ) ) 809 816 binding binding NN 816 817 . . . 818 820 We we PRP 821 828 focused focus VBD 829 832 our our PRP$ 833 840 studies study NNS 841 843 on on IN 844 847 the the DT 848 852 role role NN 853 855 of of IN 856 861 Pit-1 pit-1 NN 862 865 and and CC 866 868 of of IN 869 871 PR PR NNP 872 874 as as IN 875 884 potential potential JJ 885 900 transcriptional transcriptional JJ 901 911 regulators regulator NNS 911 912 , , , 913 918 since since IN 919 922 the the DT 923 926 POU POU NNP 927 933 domain domain NN 934 941 protein protein NN 942 947 Pit-1 pit-1 NN 948 950 is be VBZ 951 960 essential essential JJ 961 963 in in IN 964 967 the the DT 968 975 control control NN 976 978 of of IN 979 988 pituitary pituitary JJ 989 992 PRL PRL NNP 993 1003 expression expression NN 1003 1004 , , , 1005 1008 and and CC 1009 1021 progesterone progesterone NN 1022 1029 induces induce VBZ 1030 1038 decidual decidual JJ 1039 1053 transformation transformation NN 1054 1056 of of IN 1057 1060 the the DT 1061 1072 endometrial endometrial JJ 1073 1079 stroma stroma NN 1079 1080 , , , 1081 1082 a a DT 1083 1098 differentiation differentiation NN 1099 1106 process process NN 1107 1113 during during IN 1114 1119 which which WDT 1120 1123 the the DT 1124 1132 decidual decidual JJ 1133 1136 PRL PRL NNP 1137 1141 gene gene NN 1142 1144 is be VBZ 1145 1154 activated activate VBN 1154 1155 . . . 1156 1158 We we PRP 1159 1170 demonstrate demonstrate VBP 1171 1173 in in IN 1174 1175 a a DT 1176 1183 variety variety NN 1184 1186 of of IN 1187 1191 cell cell NN 1192 1197 types type NNS 1197 1198 , , , 1199 1208 including include VBG 1209 1220 lymphocytes lymphocyte NNS 1221 1224 and and CC 1225 1236 endometrial endometrial JJ 1237 1243 stroma stroma NN 1243 1244 , , , 1245 1249 that that IN 1250 1255 Pit-1 pit-1 NN 1256 1258 is be VBZ 1259 1262 not not RB 1263 1271 involved involve VBN 1272 1274 in in IN 1275 1278 the the DT 1279 1289 regulation regulation NN 1290 1292 of of IN 1293 1297 dPRL dprl NN 1298 1315 promoter/reporter promoter/reporter NN 1316 1320 gene gene NN 1321 1331 constructs construct NNS 1332 1340 carrying carry VBG 1341 1342 3 3 CD 1343 1345 kb kb NN 1346 1357 5’-flanking 5'-flanking JJ 1358 1361 DNA dna NN 1361 1362 . . . 1363 1366 Our our PRP$ 1367 1378 experiments experiment NNS 1379 1383 also also RB 1384 1388 show show VBP 1389 1393 that that IN 1394 1403 activated activate VBN 1404 1406 PR PR NNP 1407 1411 does do VBZ 1412 1415 not not RB 1416 1422 confer confer VB 1423 1429 direct direct JJ 1430 1445 transcriptional transcriptional JJ 1446 1453 control control NN 1454 1456 on on IN 1457 1460 the the DT 1461 1465 dPRL dprl NN 1466 1474 promoter promoter NN 1474 1475 . . . 1476 1480 When when WRB 1481 1483 we we PRP 1484 1492 compared compare VBD 1493 1496 the the DT 1497 1505 activity activity NN 1506 1508 of of IN 1509 1512 the the DT 1513 1524 transfected transfecte VBN 1525 1529 dPRL dprl NN 1530 1538 promoter promoter NN 1539 1541 in in IN 1542 1555 PRL-secreting prl-secreting JJ 1556 1559 and and CC 1560 1572 nonsecreting nonsecreting JJ 1573 1581 lymphoid lymphoid JJ 1582 1587 cells cell NNS 1587 1588 , , , 1589 1591 we we PRP 1592 1597 found find VBD 1598 1602 that that IN 1603 1606 the the DT 1607 1608 3 3 CD 1609 1611 kb kb NN 1612 1623 5’-flanking 5'-flanking JJ 1624 1630 region region NN 1631 1633 of of IN 1634 1637 the the DT 1638 1642 dPRL dprl NN 1643 1651 promoter promoter NN 1652 1655 did do VBD 1656 1659 not not RB 1660 1667 contain contain VB 1668 1676 elements element NNS 1677 1688 restricting restrict VBG 1689 1699 expression expression NN 1700 1702 to to TO 1703 1707 only only RB 1708 1713 those those DT 1714 1725 lymphocytes lymphocyte NNS 1726 1730 that that WDT 1731 1738 produce produce VBP 1739 1742 PRL PRL NNP 1743 1746 but but CC 1747 1754 allowed allow VBD 1755 1765 expression expression NN 1766 1768 of of IN 1769 1775 fusion fusion NN 1776 1784 reporter reporter NN 1785 1790 genes gene NNS 1791 1803 irrespective irrespective JJ 1804 1806 of of IN 1807 1810 the the DT 1811 1817 status status NN 1818 1820 of of IN 1821 1824 the the DT 1825 1835 endogenous endogenous JJ 1836 1839 PRL PRL NNP 1840 1844 gene gene NN 1844 1845 . . . 1846 1850 This this DT 1851 1854 was be VBD 1855 1857 in in IN 1858 1863 sharp sharp JJ 1864 1872 contrast contrast NN 1873 1875 to to TO 1876 1887 endometrial endometrial JJ 1888 1893 cells cell NNS 1894 1899 where where WRB 1900 1901 3 3 CD 1902 1904 kb kb NN 1905 1916 5’-flanking 5'-flanking JJ 1917 1920 DNA dna NN 1921 1930 conferred confer VBD 1931 1937 strong strong JJ 1938 1953 transcriptional transcriptional JJ 1954 1964 activation activation NN 1965 1967 on on IN 1968 1971 the the DT 1972 1976 dPRL dprl NN 1977 1985 promoter promoter NN 1986 1988 in in IN 1989 2001 decidualized decidualize VBN 2002 2013 endometrial endometrial JJ 2014 2021 stromal stromal JJ 2022 2027 cells cell NNS 2028 2036 actively actively RB 2037 2046 secreting secrete VBG 2047 2050 PRL PRL NNP 2050 2051 , , , 2052 2055 but but CC 2056 2059 did do VBD 2060 2063 not not RB 2064 2069 allow allow VB 2070 2083 transcription transcription NN 2084 2086 in in IN 2087 2103 undifferentiated undifferentiated JJ 2104 2121 non-PRL-secreting non-prl-secreting JJ 2122 2133 endometrial endometrial JJ 2134 2141 stromal stromal JJ 2142 2147 cells cell NNS 2147 2148 . . . 2149 2159 Activation Activation NNP 2160 2162 of of IN 2163 2166 the the DT 2167 2171 dPRL dprl NN 2172 2180 promoter promoter NN 2181 2190 construct construct NN 2191 2193 in in IN 2194 2199 these these DT 2200 2216 undifferentiated undifferentiated JJ 2217 2222 cells cell NNS 2223 2228 could could MD 2229 2236 however however RB 2237 2239 be be VB 2240 2247 induced induce VBN 2248 2250 by by IN 2251 2254 the the DT 2255 2263 addition addition NN 2264 2266 of of IN 2267 2271 cAMP cAMP NNP 2271 2272 , , , 2273 2275 in in IN 2276 2279 the the DT 2280 2287 absence absence NN 2288 2290 of of IN 2291 2303 progesterone progesterone NN 2303 2304 , , , 2305 2315 suggesting suggest VBG 2316 2320 that that IN 2321 2322 a a DT 2323 2329 signal signal NN 2330 2340 transduced transduce VBN 2341 2348 through through IN 2349 2352 the the DT 2353 2357 cAMP camp NN 2358 2367 signaling signaling NN 2368 2375 pathway pathway NN 2376 2378 is be VBZ 2379 2380 a a DT 2381 2388 primary primary JJ 2389 2396 inducer inducer NN 2397 2399 of of IN 2400 2408 decidual decidual JJ 2409 2412 PRL PRL NNP 2413 2417 gene gene NN 2418 2428 expression expression NN 2428 2429 . . .