Characterization of a rat uterine cell line, UIII cells:: Prolactin (PRL) expression and endogenous regulation of PRL-dependent genes; estrogen receptor β, α2-macroglobulin, and decidual PRL involving the Jak2 and Stat5 pathway

被引:21
作者
Prigent-Tessier, A
Barkai, U
Tessier, C
Cohen, H
Gibori, G
机构
[1] Univ Illinois, Dept Physiol & Biophys, Coll Med, Chicago, IL 60612 USA
[2] Inst Natl Sci Appl, INERM U352, Lab Biochim & Pharmacol, F-69100 Villeurbanne, France
关键词
D O I
10.1210/en.142.3.1242
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Decidualization of endometrial stroma in the rat induces the expression and secretion of rat decidual PRL (rdPRL). Recently, we have generated a nontransformed rat uterine stromal cell line (U-III) that decidualizes spontaneously in culture. In this report, we have established by immunocytochemistry, RT-PCR, Western blot analysis, labeled amino acid incorporation and RIA that these cells express the rat PRL messenger RNA as well as synthesize and secrete PRL. We have also cloned by RT-PCR a 403-bp complementary DNA fragment whose sequence is identical with that of rat pituitary PRL. In addition, U-III cells express the PRL receptor (PRL-R) long form, all the components involved in the PRL signal transduction pathway, estrogen receptor beta (ERP) and alpha (2)-macroglobulin (alpha (2)-MG), which are known to be PRL-regulated genes. However, when U-III, cells were treated with PRL, no regulation of these genes was observed. Moreover, in these cells, the PRL signaling components: the tyrosine kinase Jak2 and the transcription factor Stat5 were endogenously phosphorylated and their phosphorylation states were not enhanced in the presence of exogenous PRL. To examine whether the endogenously secreted PRL affects the expression of PRL-regulated genes, U-III cells were treated with either an anti-PRL receptor antibody or a Jak2 inhibitor, AG490. The anti-PRL receptor antibody decreased alpha (2)-MG expression. AG490 inhibited Jak2 and Stat5 phosphorylation, prevented Stat5 binding to its DNA consensus sequence, and also caused a dose-dependent down-regulation of alpha (2)-MG and ERP expression. In contrast, AG490 enhanced PRL mRNA levels. In summary, we have established that the U-III stromal cells of uterine origin produce PRL. Furthermore, we have shown for the first time that decidual PRL may act locally to activate the Jak2/Stat5 pathway and up-regulate important genes involved in decidual growth and placentation.
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页码:1242 / 1250
页数:9
相关论文
共 48 条
  • [1] IMPLANTATION AND DECIDUALIZATION IN RODENTS
    ABRAHAMSOHN, PA
    ZORN, TMT
    [J]. JOURNAL OF EXPERIMENTAL ZOOLOGY, 1993, 266 (06): : 603 - 628
  • [2] Prolactin receptor regulates Stat5 tyrosine phosphorylation and nuclear translocation by two separate pathways
    Ali, S
    Ali, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (13) : 7709 - 7716
  • [3] PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation
    Ali, S
    Chen, ZJ
    Lebrun, JJ
    Vogel, W
    Kharitonenkov, A
    Kelly, PA
    Ullrich, A
    [J]. EMBO JOURNAL, 1996, 15 (01) : 135 - 142
  • [4] Aplin JD., 1989, BIOL UTERUS, Vvol 20, P89, DOI DOI 10.1007/978-1-4684-5589-2_6
  • [5] Involvement of SOCS-1, the suppressor of cytokine signaling, in the prevention of prolactin-responsive gene expression in decidual cells
    Barkai, U
    Prigent-Tessier, A
    Tessier, C
    Gibori, GB
    Gibori, G
    [J]. MOLECULAR ENDOCRINOLOGY, 2000, 14 (04) : 554 - 563
  • [6] BEHRENDTSEN O, 1992, DEVELOPMENT, V114, P447
  • [7] IMMUNOCHEMICAL IDENTITY OF DECIDUALIZATION-ASSOCIATED PROTEIN AND ALPHA-2-ACUTE-PHASE MACROGLOBULIN IN THE PREGNANT RAT
    BELL, SC
    [J]. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 1979, 1 (03) : 193 - 206
  • [8] Extrapituitary prolactin: Distribution, regulation, functions, and clinical aspects
    BenJonathan, N
    Mershon, JL
    Allen, DL
    Steinmetz, RW
    [J]. ENDOCRINE REVIEWS, 1996, 17 (06) : 639 - 669
  • [9] Rescue of preimplantatory egg development and embryo implantation in prolactin receptor-deficient mice after progesterone administration
    Binart, N
    Helloco, C
    Ormandy, CJ
    Barra, J
    Clément-Lacroix, P
    Baran, N
    Kelly, PA
    [J]. ENDOCRINOLOGY, 2000, 141 (07) : 2691 - 2697
  • [10] Prolactin (PRL) and its receptor: Actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice
    Bole-Feysot, C
    Goffin, V
    Edery, M
    Binart, N
    Kelly, PA
    [J]. ENDOCRINE REVIEWS, 1998, 19 (03) : 225 - 268