Effects of castration and maturational age of male rats on the process of copper-stimulated release of luteinizing hormone releasing hormone from median eminence explants: evidence that androgens increase the affinity of the copper-interactive sites for c
Effects of castration and maturational age of male rats on the process of copper-stimulated release of luteinizing hormone releasing hormone from median eminence explants: evidence that androgens increase the affinity of the copper-interactive sites for c
复制标题
雄性大鼠去势和成熟年龄对铜刺激的中隆外植体释放黄体生成素释放激素过程的影响：雄激素增加铜相互作用位点对 c 的亲和力的证据
DOI：
10.1159/000124219
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发表时间：
1985
影响因子：
4.1
通讯作者：
Barnea,A
中科院分区：
文献类型：
--
作者：
Colombani-Vidal,M;Barnea,A
我们以前已经表明，螯合铜刺激释放促黄体激素释放激素（LHRH）从外植体的正中隆起区（MEA）在体外条件下孵育，这种刺激涉及配体特异性相互作用。在这项研究中，我们解决了这个问题：睾丸类固醇调节LHRH神经元的分泌反应铜？将从未成熟、成熟、未成熟去势和假手术大鼠中获得的MEA在不同浓度的铜存在下孵育15分钟，然后在不存在铜的情况下再孵育30分钟。我们注意到，孵育5分钟的滞后期后，LHRH释放速率以线性方式增加15分钟。此外，LHRH释放速率以及LHRH释放加速速率是铜浓度的饱和函数。当在非饱和浓度的铜（50μM）存在下进行孵育时，去势大鼠MEA释放的LHRH分数（占MEA总含量的百分比）显著（p < 0.001）低于假手术大鼠;刺激释放分别为0.9%和1.4%。同样，铜刺激释放从MEA的未成年大鼠低于从MEA的成熟大鼠。然而，当在饱和浓度的铜（100或200 µM）存在下进行孵育时，去势大鼠MEA的刺激释放百分比与假手术大鼠相似，约为2.8%。此外，我们还发现未成熟和去势大鼠MEA中LHRH含量分别显著低于成熟和假手术大鼠。为了估计这些动物MEA中LHRH可释放池的大小，我们用60 mM K+最大限度地刺激LHRH释放。结果发现，无论动物的生理状态如何，释放了约2.6%的MEA含量。这些结果表明：（1）铜与LHRH神经元上有限数量的位点相互作用;（2）睾丸类固醇通过增加这些相互作用位点对铜的亲和力来调节铜刺激的LHRH释放过程;（3）睾丸激素增加正中隆起LHRH释放池的大小，和（4）可释放库的大小与肽的MEA含量成比例，并且这种比例不是类固醇依赖性的。我们建议，睾丸类固醇调节LHRH神经元的分泌功能的两个重要方面：神经元释放LHRH的能力和铜相互作用位点对铜的亲和力。
We have previously shown that chelated copper stimulates the release of luteinizing hormone releasing hormone (LHRH) from explants of the median eminence area (MEA) incubated under in vitro conditions and that this stimulation involves a ligand-specific interaction. In this study, we addressed the question: do testicular steroids regulate the secretory response of LHRH neurons to copper? MEA, obtained from immature, mature, immature castrated and sham-operated rats, were incubated in the presence of various concentrations of copper for 15 min and then in the absence of copper for an additional period of 30 min. We noted that after a lag period of 5 min of incubation, the rate of LHRH release increased in a linear fashion for a period of 15 min. In addition, the rate of LHRHrelease as well as the rate at which LHRH release was accelerated were saturable functions of the concentration of copper. When incubation was carried out in the presence of a nonsaturating concentration of copper (50µM), the fractional amount (percent of the total MEA content) of LHRHreleased from the MEA of castrated rats was significantly (p < 0.001) lower than that from sham-operated rats; stimulated release being 0.9% and 1.4%, respectively. Similarly, copper-stimulated release from the MEA of immature rats was lower than that from the MEA of mature rats. However, when incubation was carried out in the presence of saturating concentrations of copper (100 or 200 µM), the precentage of stimulated release from the MEA of castrated rats was similar to that of sham-operated rats and it was about 2.8%. In addition, we found that LHRHcontent of the MEA of immature and castrated rats was significantly lower than that of mature and sham-operated rats, respectively. To estimate the size of the releasable pool of LHRHin the MEA of these animals, we maximally stimulated LHRH release with 60 mM K+. It was found that, regardless of the physiological state of the animals, about 2.6% of the MEA content was released. These results suggest that: (1) copper interacts with a limited number of sites on the LHRH neuron; (2) testicular steroids regulate the process of copper-stimulated release of LHRH by increasing the affinity of these interactive sites to copper; (3) testicular steroids increase the size of the releasable pool of LHRH in the median eminence, and (4) the size of the releasable pool is proportional to the MEA content of the peptide and this proportionality is not steroid-dependent. We propose that testicular steroids regulate two important aspects of the secretory function of the LHRH neuron: the capacity of the neuron to release LHRH and the affinity of the copper-interactive sites for copper.