Sex differences in brain aromatase activity: genomic and non-genomic controls.

Sex differences in brain aromatase activity: genomic and non-genomic controls.
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DOI:
10.3389/fendo.2011.00034
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发表时间:
2011
影响因子:
5.2
通讯作者:
Ball GF
Ball GF
中科院分区:
医学2区
文献类型:
--
作者:
Balthazart J;Charlier TD;Cornil CA;Dickens MJ;Harada N;Konkle AT;Voigt C;Ball GF

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雄激素在视前区芳构化为雌激素在鹌鹑和许多其他脊椎动物雄性交配的激活中起着关键作用。鹌鹑和其他鸟类中芳香化酶的表达高于啮齿动物和其他哺乳动物,这促进了对这种酶的控制和功能的研究。在相对较长的时间内(几天到几个月),脑芳香化酶活性(AA)和转录显着增加(4 - 6倍)的基因组作用的性类固醇。最初的工作表明,视前AA是男性高于女性,它被假设,这种差异生产的雌激素可能是一个关键因素,负责缺乏行为激活的女性。然而,随后的研究表明,这种酶的性别差异可能有助于但不足以解释行为的性别差异。AA,免疫反应性和mRNA浓度的研究表明,测量酶活性时观察到的性别差异,不一定观察到当一个测量mRNA浓度。差异可能反映了酶活性的翻译后控制。鹌鹑脑匀浆中的AA被磷酸化过程迅速抑制。类似的快速抑制发生在下丘脑外植体保持在体外,并暴露于影响细胞内钙浓度的药物或谷氨酸激动剂。在性互动或暴露于短期束缚应激后,体内也观察到AA的快速变化,这些雌激素产生的快速变化调节雄性性行为的表达。这些数据表明,脑雌激素显示大多数,如果不是所有的神经调质的特征,如果不是神经递质。然而,关于控制雌激素产生的这些快速变化及其行为意义的机制仍存在许多问题。
Aromatization of testosterone into estradiol in the preoptic area plays a critical role in the activation of male copulation in quail and in many other vertebrate species. Aromatase expression in quail and in other birds is higher than in rodents and other mammals, which has facilitated the study of the controls and functions of this enzyme. Over relatively long time periods (days to months), brain aromatase activity (AA), and transcription are markedly (four- to sixfold) increased by genomic actions of sex steroids. Initial work indicated that the preoptic AA is higher in males than in females and it was hypothesized that this differential production of estrogen could be a critical factor responsible for the lack of behavioral activation in females. Subsequent studies revealed, however, that this enzymatic sex difference might contribute but is not sufficient to explain the sex difference in behavior. Studies of AA, immunoreactivity, and mRNA concentrations revealed that sex differences observed when measuring enzymatic activity are not necessarily observed when one measures mRNA concentrations. Discrepancies potentially reflect post-translational controls of the enzymatic activity. AA in quail brain homogenates is rapidly inhibited by phosphorylation processes. Similar rapid inhibitions occur in hypothalamic explants maintained in vitro and exposed to agents affecting intracellular calcium concentrations or to glutamate agonists. Rapid changes in AA have also been observed in vivo following sexual interactions or exposure to short-term restraint stress and these rapid changes in estrogen production modulate expression of male sexual behaviors. These data suggest that brain estrogens display most if not all characteristics of neuromodulators if not neurotransmitters. Many questions remain however concerning the mechanisms controlling these rapid changes in estrogen production and their behavioral significance.