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芳香化酶抑制作用会降低性二态性大鼠脊髓核中的树突生长。

Aromatase inhibition reduces dendritic growth in a sexually dimorphic rat spinal nucleus.

作者信息

Burke K A, Kuwajima M, Sengelaub D R

机构信息

Program in Neural Science, Indiana University, Bloomington 47405, USA.

出版信息

J Neurobiol. 1999 Feb 15;38(3):301-12.

PMID:10022574
Abstract

The rat lumbar spinal cord contains the steroid-sensitive spinal nucleus of the bulbocavernosus (SNB), whose motoneurons innervate perineal muscles involved in copulatory reflexes. In normal males, SNB motoneuron dendrites grow exuberantly through postnatal (P) day 28. This growth is steroid dependent: Dendrites fail to grow in males castrated at P7, but grow normally in castrates treated with testosterone or its metabolites, dihydrotestosterone combined with estrogen. Treatment with either metabolite alone supports dendritic growth, but not to the level of testosterone-treated or intact males. In this study, we tested the hypothesis that aromatization of androgens to estrogens was involved in the masculine development of SNB dendrites. Motoneuron morphology was assessed in normal males and males treated daily (P7-28) with fadrozole, a potent aromatase inhibitor (0.25 mg/kg, subcutaneously) or saline vehicle (n = 4-6/group). SNB motoneurons were retrogradely labeled with cholera toxin-horseradish peroxidase at P28 (when dendritic length is normally maximal) and reconstructed in three dimensions. Comparable labeling was seen across groups; it was equivalent in both the rostrocaudal and radial extents. However, dendritic lengths in fadrozole-treated males were significantly below those of intact or saline-treated males. Neither SNB somata size nor target muscle weight differed across groups. These results suggest that aromatization of androgens to estrogens is necessary for development of masculine SNB dendritic morphology.

摘要

大鼠腰段脊髓包含球海绵体肌的类固醇敏感脊髓核(SNB),其运动神经元支配参与交配反射的会阴肌。在正常雄性大鼠中,SNB运动神经元树突在出生后(P)第28天前旺盛生长。这种生长依赖于类固醇:在P7阉割的雄性大鼠中,树突无法生长,但在用睾酮或其代谢产物、二氢睾酮与雌激素联合处理的去势大鼠中,树突正常生长。单独使用任何一种代谢产物进行处理都能支持树突生长,但达不到睾酮处理组或完整雄性大鼠的水平。在本研究中,我们测试了雄激素向雌激素的芳香化作用参与SNB树突男性化发育这一假说。在正常雄性大鼠以及每天(P7 - 28)用强效芳香化酶抑制剂法倔唑(0.25 mg/kg,皮下注射)或生理盐水载体处理的雄性大鼠中评估运动神经元形态(每组n = 4 - 6)。在P28(此时树突长度通常最大)用霍乱毒素 - 辣根过氧化物酶对SNB运动神经元进行逆行标记,并进行三维重建。各组间可见相当的标记;在前后和径向范围上都是等效的。然而,法倔唑处理的雄性大鼠的树突长度显著低于完整或生理盐水处理的雄性大鼠。各组间SNB胞体大小和靶肌肉重量均无差异。这些结果表明,雄激素向雌激素的芳香化作用对于男性化SNB树突形态的发育是必要的。

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Castration-induced upregulation of muscle ERα supports estrogen sensitivity of motoneuron dendrites in a sexually dimorphic neuromuscular system.
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