Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus
Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus
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DOI：
10.1111/j.1460-9568.2003.03029.x
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发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Smith, PG
中科院分区：
文献类型：
--
作者：
Krizsan-Agbas, D;Pedchenko, T;Smith, PG
成年啮齿动物子宫交感神经循环重构。终末交感轴突在雌激素水平升高时退化，在雌激素水平下降时再生。本研究探讨了神经营养因子在雌激素介导的子宫交感神经重构中的作用。去卵巢雌性大鼠注射雌激素后24 h不影响子宫NT-3水平，并增加子宫内膜NGF蛋白，提示NGF或NT-3的减少与雌激素诱导的去神经支配无关。雌激素升高了肌层和子宫内膜BDNF蛋白和mRNA的表达。为了评估BDNF的增加是否会影响子宫对交感神经节外植体的接受性，我们将交感神经节外植体与子宫肌层共培养。去卵巢大鼠的子宫肌层在无雌激素条件下诱导神经细胞发生，当培养基中加入BDNF时，这种情况被消除。卵巢切除后的子宫肌层诱导的神经新生被雌激素抑制，并被BDNF功能阻断抗体恢复。为了确定雌激素抑制交感神经突生长是否需要靶向BDNF的合成，我们将野生型小鼠和重组BDNF基因突变纯合子或杂合子小鼠的子宫与大鼠交感神经节一起培养。雌激素可抑制野生型子宫的神经发生。纯合子BDNF突变体子宫的神经突形成不受雌激素的影响，但低于野生型小鼠。BDNF杂合突变小鼠的子宫，其BDNF合成减少，显示正常的神经生成特性，但不受雌激素的影响。这些发现表明，雌激素通过调节BDNF合成来改变啮齿动物子宫的神经生成特性，从而抑制交感神经突的生长。
Sympathetic innervation of the adult rodent uterus undergoes cyclic remodelling. Terminal sympathetic axons degenerate when oestrogen levels rise and regenerate when oestrogen levels decline. This study examined the role of neurotrophins in oestrogen-mediated uterine sympathetic nerve remodelling. Oestrogen injection of ovariectomized female rats did not affect uterine NT-3 levels 24 h postinjection, and increased endometrial NGF protein, indicating that reduced NGF or NT-3 is not responsible for the oestrogen-induced denervation. Oestrogen also raised BDNF protein and mRNA in myometrium and endometrium. To assess whether increased BDNF affects uterine receptivity to sympathetic outgrowth, sympathetic ganglion explants were co-cultured with myometrium. Myometrium from ovariectomized rats induced neuritogenesis in oestrogen-free conditions, and this was abolished when BDNF was added to the medium. Neuritogenesis induced by ovariectomized myometrium was suppressed by oestrogen, and restored by a BDNF function-blocking antibody. To determine if target BDNF synthesis is required for oestrogen to suppress sympathetic neurite outgrowth, uteri from wild-type mice and mice homozygous or heterozygous for recombinant mutations of the BDNF gene were cultured with rat sympathetic ganglia. Neuritogenesis induced by wild-type uteri was diminished by oestrogen. Neurite formation in the presence of homozygous BDNF mutant uteri was not affected by oestrogen, but was lower than that of wild-type mice. Uteri from mice heterozygous for the BDNF mutation, who have reduced BDNF synthesis, showed normal neuritogenic properties, but were not affected by oestrogen. These findings suggest that oestrogen alters neuritogenic properties of the rodent uterus by regulating BDNF synthesis, which inhibits sympathetic neurite outgrowth.