LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis.
LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis.
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DOI：
10.1210/en.2010-0208
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发表时间：
2010-10
期刊：
影响因子：
4.8
通讯作者：
Yingjie Wu;Hao-shu Luo;Jiali Liu;Duo Kang;A. McNeilly;S. Cui
中科院分区：
文献类型：
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作者：
Yingjie Wu;Hao-shu Luo;Jiali Liu;Duo Kang;A. McNeilly;S. Cui
Lin-11、Isl-1和Mec-3（LIM）同源域转录因子Isl-1已被报道参与小鼠胚胎发育早期的垂体发育。我们最近的研究表明，Isl-1主要位于垂体促性腺激素在整个垂体发育，并持续到成年。Isl-1在垂体中表达的生理功能及其相关机制尚不清楚。本研究的目的是验证Isl-1通过激活FSHβ和LHβ基因表达参与调节垂体促性腺激素（FSH/LH）产生的假说。我们已经证明Isl-1激活LβT2细胞中FSHβ和LHβ亚基启动子和内源性基因转录。此外，Isl-1过表达显著增加FSH的合成和分泌，但不增加LH。当同源结构域或LIM 1结构域突变时，未观察到Isl-1的作用。这表明Isl-1对FSHβ和LHβ的诱导是通过Isl-1与DNA序列的直接和间接结合。GnRH、激活素和瘦素作用后，LβT2细胞Isl-1表达水平上调。RNA干扰诱导Isl-1基因敲低可显著降低瘦素的作用，但对GnRH和激活素刺激LH和FSH的作用无明显影响。上述结果表明，LIM同源域转录因子Isl-1具有促进FSHβ/LHβ基因转录的功能，并介导了瘦素对促性腺激素合成的影响。
The Lin-11, Isl-1, and Mec-3 (LIM) homeodomain transcription factor Isl-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Our recent studies have shown that Isl-1 is mainly located in the pituitary gonadotropes throughout pituitary development and persists to adulthood. We still do not know the physiological functions of Isl-1 expression and its related mechanisms in the pituitary gland. The aim of the present study was to examine the hypothesis that Isl-1 is involved in regulating pituitary gonadotropin hormone (FSH/LH) production by activating FSHβ and LHβ gene expressions. We have shown that Isl-1 activates FSHβ and LHβ subunit promoters and endogenous gene transcription in LβT2 cells. In addition, Isl-1 overexpression significantly increased FSH synthesis and secretion but not LH. The actions of Isl-1 were not observed when the homeodomain or LIM1 domains are mutated. This demonstrates that Isl-1 induction of FSHβ and LHβ is by both direct and indirect binding of Isl-1 to DNA sequences. Furthermore, Isl-1 expressional level was up-regulated in LβT2 cells after exposure to GnRH, activin, and leptin. However, RNA interference-induced knockdown of Isl-1 significantly reduced the effect of leptin but did not obviously influence the stimulating effects of GnRH and activin on LH and FSH production. In conclusion, the results demonstrate that the LIM-homeodomain transcription factor Isl-1 functions to increase FSHβ/LHβ gene transcription, and mediates the effects of leptin on gonadotropin synthesis.