Insulin-Like Growth Factor-I Activates KiSS-1 Gene Expression in the Brain of the Prepubertal Female Rat
Insulin-Like Growth Factor-I Activates KiSS-1 Gene Expression in the Brain of the Prepubertal Female Rat
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DOI：
10.1210/en.2008-0954
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Dees, W. Les
中科院分区：
文献类型：
--
作者：
Hiney, Jill K.;Srivastava, Vinod K.;Dees, W. Les
KiSS-1基因表达随着青春期的临近而增加，其肽产物kisspeptins参与青春期LHRH的分泌。然而，导致KiSS-1表达增加的因素尚未确定;因此，本研究的目的是评估IGF-I是否可以诱导青春期前雌性大鼠该基因的转录。将IGF-I或盐水集中给予未成熟大鼠，在2、4和6 h后处死。实时荧光定量PCR显示，IGF-I在6 h时可诱导（P < 0.01）包含前腹侧室周核（AVPV）和弓状核（ARC）的组织片段中KiSS-1基因表达。随后，分离AVPV和ARC核以评估是否可以识别区域特异性效应。注射IGF-I后6 h，AVPV核KiSS-1基因表达显著增加（P < 0.01），ARC核KiSS-1基因表达无明显变化。血清雌二醇（E-2）水平在IGF-I后的任何时间点都没有改变，表明观察到的KiSS-1表达增加不是由E2升高引起的。此外，当全身给予IGF-I时，进一步证明了IGF-I诱导AVPV核中KiSS-1基因表达的作用。E2似乎起着重要的容许作用，因为卵巢切除后1天的大鼠对IGF-I的反应是KiSS-1表达增加（P < 0.01），而卵巢切除后20天，当E2水平下降到低于测定灵敏度时，IGF-I不能诱导KiSS-1表达。IGF-I受体拮抗剂JB-1阻断了IGF-I诱导的KiSS-1表达增加，进一步证明了IGF-I的作用。总的来说，这些数据表明，IGF-I是一个激活剂的KiSS-1基因在青春期前的雌性大鼠。（内分泌学150：376-384，2009）
KiSS-1 gene expression has been shown to increase as puberty approaches, and its peptide products, kisspeptins, are involved in LHRH secretion at puberty. Factors contributing to increased KiSS-1 expression, however, have not been identified; thus, the purpose of this study was to assess whether IGF-I could induce transcription of this gene in prepubertal female rats. IGF-I or saline was centrally administered to immature rats that were killed 2, 4, and 6 h later. Real-time PCR revealed that IGF-I induced (P < 0.01) KiSS-1 gene expression at 6 h in a tissue fragment that contained both the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. Subsequently, the AVPV and ARC nuclei were separated to assess whether region-specific effects could be identified. IGF-I stimulated (P < 0.01) KiSS-1 gene expression in the AVPV nucleus at 6 h after injection, with no change observed in the ARC nucleus. Serum estradiol (E-2) levels were not altered at any time point after IGF-I, demonstrating that the increased KiSS-1 expression observed was not caused by an elevation in E2. Additionally, the IGF-I action to induce KiSS-1 gene expression in the AVPV nucleus was further demonstrated when the IGF-I was administered systemically. E2 appears to play an important permissive role because 1-d ovariectomized rats responded to IGF-I with increased (P < 0.01) KiSS-1 expression, whereas, 20 d after ovariectomy, when the E2 levels had fallen below assay sensitivity, the IGF-I was unable to induce KiSS-1 expression. The IGF-I effect was further demonstrated by showing that the IGF-I receptor antagonist, JB-1, blocked the IGF-I-induced increase in KiSS-1 expression. Collectively, these data indicate that IGF-I is an activator of the KiSS-1 gene in the prepubertal female rat. (Endocrinology 150: 376-384, 2009)