Maximal expression of Foxl2 in pituitary gonadotropes requires ovarian hormones.
Maximal expression of Foxl2 in pituitary gonadotropes requires ovarian hormones.
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DOI：
10.1371/journal.pone.0126527
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nilson JH
中科院分区：
文献类型：
--
作者：
Herndon MK;Nilson JH
促性腺激素释放激素（GnRH）和激活素调节FSH的合成并最终调节生育力。最近的体内研究将SMAD 4和FOXL 2作为激活素信号传导的主要转录介质，它们共同作用并独立于GnRH调节Fshb基因表达和女性生育力。卵巢激素通过负反馈和正反馈调节GnRH及其受体（GNRHR）。相比之下，卵巢激素在调节激活素、激活素受体和激活素信号通路的组分（包括SMAD 4和FOXL 2）中的作用仍然研究不足。激活素及其许多信号中间体的广泛分布使得分析卵巢激素对其在促性腺细胞（五种垂体细胞类型之一）中合成的影响变得复杂。我们规避了这种并发症，通过使用转基因模型，允许选择性地从完整的女性和卵巢切除的女性促性腺激素治疗或不治疗GnRH拮抗剂的多聚核糖体的隔离。这种模式允许评估卵巢激素反馈，并区分独立或依赖于GnRH的反应。令人惊讶的是，我们的研究结果表明，促性腺激素细胞中的Foxl 2水平在没有卵巢输入的情况下显著下降，并且独立于GnRH。编码激活素信号传导途径的其他成员的基因的表达不受卵巢激素反馈损失的影响，突出了它们对Foxl 2的选择性作用。Gnrhr（FOXL 2的已知靶标）的表达也在卵巢切除术后下降，这与Foxl 2表达减少和卵巢激素损失一致。相反，Fshb mRNA在卵巢切除术后由于GnRH的代偿性输入增加而显著增加。总之，这些数据表明，卵巢激素调节Foxl 2的表达，从而扩大由下丘脑-垂体-性腺轴控制的基因数量，最终决定生殖健康。
Gonadotropin-releasing hormone (GnRH) and activin regulate synthesis of FSH and ultimately fertility. Recent in vivo studies cast SMAD4 and FOXL2 as master transcriptional mediators of activin signaling that act together and independently of GnRH to regulate Fshb gene expression and female fertility. Ovarian hormones regulate GnRH and its receptor (GNRHR) through negative and positive feedback loops. In contrast, the role of ovarian hormones in regulating activin, activin receptors, and components of the activin signaling pathway, including SMAD4 and FOXL2, remains understudied. The widespread distribution of activin and many of its signaling intermediates complicates analysis of the effects of ovarian hormones on their synthesis in gonadotropes, one of five pituitary cell types. We circumvented this complication by using a transgenic model that allows isolation of polyribosomes selectively from gonadotropes of intact females and ovariectomized females treated with or without a GnRH antagonist. This paradigm allows assessment of ovarian hormonal feedback and distinguishes responses that are either independent or dependent on GnRH. Surprisingly, our results indicate that Foxl2 levels in gonadotropes decline significantly in the absence of ovarian input and independently of GnRH. Expression of the genes encoding other members of the activin signaling pathway are unaffected by loss of ovarian hormonal feedback, highlighting their selective effect on Foxl2. Expression of Gnrhr, a known target of FOXL2, also declines upon ovariectomy consistent with reduced expression of Foxl2 and loss of ovarian hormones. In contrast, Fshb mRNA increases dramatically post-ovariectomy due to increased compensatory input from GnRH. Together these data suggest that ovarian hormones regulate expression of Foxl2 thereby expanding the number of genes controlled by the hypothalamic-pituitary-gonadal axis that ultimately dictate reproductive fitness.
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影响因子：
--
作者：
Couse, JF;Yates, MM;Korach, KS
通讯作者：
Korach, KS
影响因子：
3.6
作者：
Eozenou, Caroline;Carvalho, Anais Vitorino;Sandra, Olivier
通讯作者：
Sandra, Olivier
影响因子：
3.6
作者：
FALLEST, PC;TRADER, GL;SHUPNIK, MA
通讯作者：
SHUPNIK, MA
影响因子：
3.5
作者：
Baron, D;Cocquet, J;Veitia, RA
通讯作者：
Veitia, RA
DOI：
10.1097/med.0b013e32832d88fb
发表时间：
2009-08
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Ciccone NA;Kaiser UB
通讯作者：
Kaiser UB