Androgens stimulate the morphological maturation of embryonic hypothalamic aromatase-immunoreactive neurons in the mouse
Androgens stimulate the morphological maturation of embryonic hypothalamic aromatase-immunoreactive neurons in the mouse
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DOI：
10.1016/s0165-3806(96)00170-8
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发表时间：
1997-01-02
期刊：
影响因子：
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通讯作者：
Hutchison, JB
中科院分区：
文献类型：
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作者：
Beyer, C;Hutchison, JB
性腺类固醇作为啮齿动物大脑的发育因子发挥着重要作用，并与神经结构的性别分化有关。雌激素与中枢神经元的存活和可塑性有关，从而调节与生殖功能相关的下丘脑和边缘结构的发育。除了雌激素外，雄激素也对中枢神经系统的成熟做出积极贡献，我们最近发现，雄激素通过刺激雌激素形成中关键酶 Arom 的表达，刺激培养的下丘脑芳香酶免疫反应性 (Arom-IR) 神经元的受体介导的功能分化。在本研究中，我们研究了雄激素是否能够影响下丘脑 Arom-IR 神经元的形态分化。与雌激素不同，雄激素治疗通过增加神经突生长和分支、胞体大小和干突数量来刺激培养的胚胎下丘脑 Arom-IR 细胞的形态分化。这种效应是大脑区域和递质表型特异性的：皮质 Arom-IR 神经元和下丘脑 GABA 能神经元都对雄激素没有反应。此外，形态发生效应取决于雄激素受体（AR）激活，因为形态变化被氟他胺完全抑制。下丘脑 Arom-IR 神经元的双重标记揭示了相当数量的细胞共表达 AR，而皮质 Arom-IR 细胞没有标记 AR。我们的数据表明，雄激素作为下丘脑 Arom-IR 细胞发育的形态发生信号，因此可能有效影响下丘脑 Arom 系统的可塑性和突触连接。
Gonadal steroids play an important role as developmental factors for the rodent brain and are implicated in the sexual differentiation of neural structures. Estrogens have been linked to survival and plasticity of central neurons, thereby regulating the development of hypothalamic and limbic structures associated with reproductive functions. Besides estrogens, androgens also contribute actively to CNS maturation, We have shown recently that androgens stimulate the receptor-mediated functional differentiation of cultured hypothalamic aromatase-immunoreactive (Arom-IR) neurons by stimulating the expression of Arom, the key enzyme in estrogen formation. In the present study, we investigated whether androgens are capable of influencing morphological differentiation of hypothalamic Arom-IR neurons. Androgen treatment, unlike estrogen, stimulated the morphological differentiation of cultured embryonic hypothalamic Arom-IR cells by increasing neurite outgrowth and branching, soma size, and the number of stem processes. This effect was brain region- and transmitter phenotype-specific: neither cortical Arom-IR neurons nor hypothalamic GABAergic neurons responded to androgens. Moreover, morphogenetic effects depended on androgen receptor (AR) activation, since morphological changes were completely inhibited by flutamide. Double-labeling of hypothalamic Arom-IR neurons revealed a considerable number of cells coexpressing AR, whereas cortical Arom-IR cells did not label for AR. Our data demonstrate that androgens function as morphogenetic signals for developing hypothalamic Arom-IR cells, thus being potentially effective in influencing plasticity and synaptic connectivity of hypothalamic Arom-systems.