Absil P, Baillien M, Ball G F, Panzica G C, Balthazart J
Center for Cellular and Molecular Neurobiology, Research Group in Behavioral Neuroendocrinology, University of Liège, 17 place Delcour, B-4020, Liège, Belgium.
Brain Res Brain Res Rev. 2001 Nov;37(1-3):38-58. doi: 10.1016/s0165-0173(01)00122-9.
This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and aromatase mRNA synthesis in the preoptic area are enhanced by testosterone and its metabolite estradiol, but estradiol receptors of the alpha subtype are not regularly colocalized with aromatase. Estradiol receptors of the beta subtype are present in the preoptic area but it is not yet known whether these receptors are colocalized with aromatase. The regulation by estrogen of aromatase activity may be, in part, trans-synaptically mediated, in a manner that is reminiscent of the ways in which steroids control the activity of gonadotropic hormone releasing hormone neurons. Aromatase-immunoreactive neurons are surrounded by dense networks of vasotocin-immunoreactive and tyrosine hydroxylase-immunoreactive fibers and punctate structures. These inputs are in part steroid-sensitive and could therefore mediate the effects of steroids on aromatase activity. In vivo pharmacological experiments indicate that catecholaminergic depletions significantly affect aromatase activity presumably by modulating aromatase transcription. In addition, in vitro studies on brain homogenates or on preoptic-hypothalamic explants show that aromatase activity can be rapidly modulated by a variety of dopaminergic compounds. These effects do not appear to be mediated by the membrane dopamine receptors and could involve changes in the phosphorylation state of the enzyme. Together, these results provide converging evidence for a direct control of aromatase activity by catecholamines consistent with the anatomical data indicating the presence of a catecholaminergic innervation of aromatase cells. These dopamine-induced changes in aromatase activity are observed after several hours or days and presumably result from changes in aromatase transcription but rapid non-genomic controls have also been identified. The potential significance of these processes for the physiology of reproduction is critically evaluated.
本综述总结了目前关于鹌鹑视前区芳香化酶活性调控机制的知识,视前区是大脑中在生殖控制方面起关键作用的区域。视前区的芳香化酶和芳香化酶mRNA合成会被睾酮及其代谢产物雌二醇增强,但α亚型的雌二醇受体并不总是与芳香化酶共定位。β亚型的雌二醇受体存在于视前区,但这些受体是否与芳香化酶共定位尚不清楚。雌激素对芳香化酶活性的调节可能部分是通过跨突触介导的,其方式类似于类固醇控制促性腺激素释放激素神经元活性的方式。芳香化酶免疫反应性神经元被血管紧张素免疫反应性和酪氨酸羟化酶免疫反应性纤维及点状结构的密集网络所包围。这些输入部分对类固醇敏感,因此可能介导类固醇对芳香化酶活性的影响。体内药理学实验表明,儿茶酚胺能耗竭可能通过调节芳香化酶转录显著影响芳香化酶活性。此外,对脑匀浆或视前区 - 下丘脑外植体的体外研究表明,多种多巴胺能化合物可快速调节芳香化酶活性。这些作用似乎不是由膜多巴胺受体介导的,可能涉及酶磷酸化状态的变化。总之,这些结果为儿茶酚胺对芳香化酶活性的直接控制提供了一致的证据,这与解剖学数据表明存在芳香化酶细胞的儿茶酚胺能神经支配一致。这些多巴胺诱导的芳香化酶活性变化在数小时或数天后观察到,推测是由芳香化酶转录变化引起的,但也已确定存在快速非基因组控制。对这些过程在生殖生理学中的潜在意义进行了批判性评估。