Suppression of prolactin-induced signal transducer and activator of transcription 5b signaling and induction of suppressors of cytokine signaling messenger ribonucleic acid in the hypothalamic arcuate nucleus of the rat during late pregnancy and lactation
Suppression of prolactin-induced signal transducer and activator of transcription 5b signaling and induction of suppressors of cytokine signaling messenger ribonucleic acid in the hypothalamic arcuate nucleus of the rat during late pregnancy and lactation
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DOI：
10.1210/en.2005-0755
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发表时间：
2006-10-01
期刊：
影响因子：
4.8
通讯作者：
Grattan, David R.
中科院分区：
文献类型：
--
作者：
Anderson, Greg M.;Beijer, Paulien;Grattan, David R.
在妊娠晚期和哺乳期，通过负反馈调节催乳素分泌的结节漏斗多巴胺 (TIDA) 神经元响应催乳素而产生多巴胺的能力降低，导致高催乳素血症。由于催乳素诱导的这些神经元中多巴胺合成的激活需要 Janus 激酶/信号转导器和转录激活剂 5b (STAT5b) 信号通路，因此我们研究了催乳素诱导的 STAT5b 信号在哺乳期间是否减少，以及细胞因子信号抑制 (SOCS) mRNA 的诱导是否发生在此时和妊娠后期。哺乳期间，与动情期大鼠相比，外源催乳素诱导STAT5磷酸化和STAT5b核转位的能力明显降低。在非妊娠雌性大鼠中，用羊催乳素进行急性治疗可显着增加弓状核微穿孔中 SOCS-1 和 -3 以及细胞因子诱导的含 SH2 蛋白 mRNA 的水平。妊娠第 22 天时，SOCS-1 和 SOCS-3 mRNA 水平是 G20 时的 10 倍。 SOCS-1和-3以及细胞因子诱导的含SH2蛋白的mRNA水平在哺乳期第7天也升高。此时，多巴胺能活性降低并且大鼠患有高催乳素血症。溴隐亭预处理（妊娠第 22 天）或幼仔去除（哺乳第 7 天）可防止 SOCS mRNA 的高水平，从而将循环催乳素抑制至基础水平。这些结果表明，在妊娠末期，催乳素失去激活 STAT5b 的能力，这与 SOCS mRNA 的增加有关。这种刺激途径的丧失可能是导致妊娠晚期和哺乳期特征的结节漏斗部多巴胺神经元多巴胺输出减少和高催乳素血症的原因。母体高水平的 SOCS mRNA 似乎依赖于催乳素，可能通过 STAT5b 的替代信号通路发挥作用。
During late pregnancy and lactation, the tuberoinfundibular dopamine (TIDA) neurons that regulate prolactin secretion by negative feedback become less able to produce dopamine in response to prolactin, leading to hyperprolactinemia. Because prolactin-induced activation of dopamine synthesis in these neurons requires the Janus kinase/signal transducer and activator of transcription 5b (STAT5b) signaling pathway, we investigated whether prolactin-induced STAT5b signaling is reduced during lactation and whether induction of suppressors of cytokine signaling (SOCS) mRNAs occur at this time and in late pregnancy. During lactation, the ability of exogenous prolactin to induce STAT5 phosphorylation and STAT5b nuclear translocation was markedly reduced when compared with diestrous rats. In nonpregnant female rats, acute treatment with ovine prolactin markedly increased levels of SOCS-1 and -3 and cytokine-inducible SH2-containing protein mRNA in arcuate nucleus micropunches. On gestation d 22, SOCS-1 and SOCS-3 mRNA levels were 10-fold that on G20. SOCS-1 and -3 and cytokine-inducible SH2-containing protein mRNA levels were also elevated on lactation d 7. At these times, dopaminergic activity was decreased and the rats were hyperprolactinemic. The high levels of SOCS mRNA were prevented by bromocriptine pretreatment (gestation d 22) or pup removal (lactation d 7), which suppressed circulating prolactin to basal levels. These results demonstrate that around the end of pregnancy, prolactin loses the ability to activate STAT5b, associated with an increase in SOCS mRNAs. The loss of this stimulating pathway may underlie the reduced tuberoinfundibular dopamine neuron dopamine output and hyperprolactinemia that characterizes late pregnancy and lactation. The high maternal levels of SOCS mRNAs appear to be dependent on prolactin, presumably acting through an alternative signaling pathway to STAT5b.