A direct dopaminergic control of aromatase activity in the quail preoptic area
A direct dopaminergic control of aromatase activity in the quail preoptic area
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DOI：
10.1016/s0960-0760(97)00080-0
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发表时间：
1997-09-01
影响因子：
4.1
通讯作者：
Balthazart, J
中科院分区：
文献类型：
--
作者：
Baillien, M;Balthazart, J
在鹌鹑视前区（POA）的解剖学和药理学数据表明，儿茶酚胺可能参与控制睾酮（T）芳构化为雌激素。然而，介导这种酶活性控制的生化机制尚未探索。本研究进行调查是否儿茶酚胺，多巴胺（DA）和去甲肾上腺素（NE）能够直接影响芳香化酶活性（AA）在体外孵育过程中测定的POA匀浆。通过测量[1 β-H-3]-雄烯二酮产生的氚水，定量测定成年雄性日本鹌鹑POA-下丘脑中的AA。酶活性与孵育时间和匀浆中蛋白质含量呈线性关系。它表现出典型的米氏动力学，表观Km为2.8 nM，V-max为266.6 fmol h（-1）mg湿重（-1）。然后在25 nM的底物浓度下测量AA。在两种浓度10（-3）和10（-6）M的儿茶酚胺及其某些受体激动剂或拮抗剂存在下。去甲肾上腺素和哌唑嗪（α 1-肾上腺素能拮抗剂）在两种浓度下对AA没有影响或影响非常有限。相比之下，DA和一些D1和/或D2受体激动剂（阿扑吗啡[D1/D2]、SKF-38393 [D1]和RU-24213 [D2]）在10（-3）M浓度下可使AA降低40%至70%。一种D2受体拮抗剂也对AA（舒必利）产生了主要抑制作用，而其他拮抗剂（SCH-23390 [D1]、螺哌隆[D2]、匹莫齐特[D2]）没有显著作用或仅产生中度酶活性降低，两种DA间接激动剂氨甲酰二酸和诺米芬辛也是如此。激动剂的抑制作用未被活性较低的拮抗剂SCH-23390 [D1]或螺哌隆[D2]拮抗。总之，这些结果表明，抑制作用不涉及DA或其激动剂/拮抗剂与多巴胺能受体介导cAMP浓度变化的特异性结合。这一结论也得到了观察结果的支持，即添加二丁酰cAMP不会改变脑AA。DA和多巴胺能药物更可能通过对酶的直接作用抑制AA，这由DA和SKF-38393对AA的抑制的竞争性性质（Ki分别为59和84 μ M）所表明。这种作用的功能意义仍有待证实，但这种机制可能代表了一种重要的生理途径，通过这种途径，神经递质可以迅速影响类固醇依赖性过程，如雌激素的神经合成。这将为环境刺激影响生殖行为和生理提供一种手段。(C)1997 Elsevier Science Ltd.保留所有权利。
In the quail preoptic area (POA) anatomical and pharmacological data suggest that catecholamines may be implicated in the control of testosterone (T) aromatization into estrogens. The biochemical mechanism(s) mediating this control of the enzyme activity is (are) however unexplored. The present studies were carried out to investigate whether the catecholamines, dopamine (DA) and norepinephrine (NE) are able to directly affect aromatase activity (AA) measured during in vitro incubations of POA homogenates. AA was quantified in the POA-hypothalamus of adult male Japanese quail by measuring the tritiated water production from [1 beta-H-3]-androstenedione. Enzyme activity was linear as a function of the incubation time and of the protein content of homogenates. It exhibited a typical Michaelis-Menten kinetics, with an apparent K-m of 2.8 nM and a V-max of 266.6 fmol h(-1) mg wet weight(-1). AA was then measured at a substrate concentration of 25 nM. in the presence of catecholamines and some of their receptor agonists or antagonists, at two concentrations, 10(-3) and 10(-6) M. Norepinephrine and prazosin (alpha 1-adrenergic antagonist) had no or very limited effects on AA at both concentrations. In contrast, DA and some D1 and/or D2 receptor agonists (apomorphine[D1/D2], SKF-38393 [D1] and RU-24213 [D2]) depressed AA by 40 to 70% at the 10(-3) M concentration. One D2 receptor antagonist also produced a major inhibition of AA (sulpiride) while other antagonists either had no significant effect or only produced moderate decreases in enzyme activity (SCH-23390 [D1], spiperone [D2], pimozide [D2]) as did two DA indirect agonists, amfonelic acid and nomifensine. The inhibitory effect of the agonists was not antagonized by the less active antagonists, SCH-23390 [D1] or spiperone [D2]. Taken together these results suggest that the inhibitory effects do not involve specific binding of DA or its agonists/antagonists to dopaminergic receptors mediating changes in cAMP concentration. This conclusion is also supported by the observation that addition of dibutyryl cAMP did not change brain AA. It appears more likely that DA and dopaminergic drugs inhibit AA by a direct effect on the enzyme, as suggested by the competitive nature of DA and SKF-38393 inhibition of AA (K-i's of 59 and 84 mu M, respectively). The functional significance of this effect should still be demonstrated but this mechanism may represent an important physiological pathway through which neurotransmitters could rapidly affect steroid-dependent processes such as the neural synthesis of estrogens. This would provide a mean by which environmental stimuli could affect reproductive behavior and physiology. (C) 1997 Elsevier Science Ltd. All rights reserved.