A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3 expression in the corpus luteum of the pregnant rat: a potential new mechanism in luteolysis.
A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3 expression in the corpus luteum of the pregnant rat: a potential new mechanism in luteolysis.
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发表时间：
2002
期刊：
影响因子：
4.8
通讯作者：
J. Curlewis;S. Tam;P. Lau;D. H. L. Kusters;J. Barclay;S. T. Anderson;M. Waters
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作者：
J. Curlewis;S. Tam;P. Lau;D. H. L. Kusters;J. Barclay;S. T. Anderson;M. Waters
PRL和胎盘催乳素（PL）在维持啮齿动物妊娠期黄体中起关键作用。细胞因子信号转导抑制因子（SOCS）已被证明可以降低细胞对细胞因子（包括PRL）的敏感性，因此在这里我们讨论了前列腺素F（2 α）（PGF（2 α））诱导的黄体溶解是否可能上调SOCS蛋白以抑制PRL信号转导的问题。在第19天妊娠大鼠中，氯前列醇（一种PGF（2 α）类似物）快速诱导SOCS-3转录，并在较小程度上诱导SOCS-1转录。我们还发现增加SOCS-3蛋白在卵巢免疫印迹和黄体免疫组化。通过凝胶位移和免疫组织化学测定，在注射氯前列醇后10分钟，STAT 3酪氨酸磷酸化增加，SOCS-3表达增加，并维持4小时。SOCS-3的诱导伴随着活性STAT 5的急剧下降，如通过凝胶移位测定和核定位的STAT 5的损失所确定的。氯前列醇给药后4小时，黄体对PRL给药引起的STAT 5刺激不敏感，这不是由于PRL受体下调所致。因此，PGF（2 α）诱导SOCS-3可能是通过快速抑制PL促黄体支持而引发黄体溶解的重要因素。
PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and so here we have addressed the issue of whether luteolysis induced by prostaglandin F(2alpha) (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.