Krizsan-Agbas D, Pedchenko T, Hasan W, Smith P G
Department of Molecular and Integrative Physiology, Kansas University Medical Center, Kansas City, KS 66160, USA.
Eur J Neurosci. 2003 Nov;18(10):2760-8. doi: 10.1111/j.1460-9568.2003.03029.x.
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.
成年啮齿动物子宫的交感神经支配会经历周期性重塑。当雌激素水平升高时，终末交感神经轴突会退化，而当雌激素水平下降时则会再生。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塑中的作用。对去卵巢雌性大鼠注射雌激素，在注射后24小时对子宫NT - 3水平没有影响，但增加了子宫内膜NGF蛋白，这表明NGF或NT - 3减少并非雌激素诱导去神经支配的原因。雌激素还提高了子宫肌层和子宫内膜中BDNF蛋白和mRNA的水平。为了评估BDNF增加是否影响子宫对交感神经生长的反应性，将交感神经节外植体与子宫肌层共同培养。去卵巢大鼠的子宫肌层在无雌激素条件下可诱导神经突生成，而当向培养基中添加BDNF时，这种作用被消除。去卵巢子宫肌层诱导的神经突生成受到雌激素抑制，并可被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组织BDNF合成，将野生型小鼠以及BDNF基因重组突变纯合或杂合的小鼠子宫与大鼠交感神经节一起培养。野生型子宫诱导的神经突生成受到雌激素抑制。纯合BDNF突变子宫存在时的神经突形成不受雌激素影响，但低于野生型小鼠。BDNF突变杂合小鼠的子宫BDNF合成减少，其显示出正常的神经突生成特性，但不受雌激素影响。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突生成特性，从而抑制交感神经突生长。
