Hormonal regulation of peripheral benzodiazepine receptor binding properties is mediated by subunit interaction.
Hormonal regulation of peripheral benzodiazepine receptor binding properties is mediated by subunit interaction.
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外周苯二氮卓受体结合特性的激素调节是由亚基相互作用介导的。
作者：
I. Golani;Abraham Weizman;S. Leschiner;I. Spanier;N. Eckstein;R. Limor;J. Yanai;K. Maaser;H. Scherübl;G. Weisinger;M. Gavish
外周苯二氮卓类受体(PBR)由三个亚基组成，分子量分别为18、30和32 kDa。许多生理功能都归因于PBR，包括调节类固醇的生成。此外，PBR本身也受到荷尔蒙的调节。在目前的研究中，我们研究了女性性激素在类固醇生成和非类固醇生成组织中调节PBR表达的作用。为此，成年雌性大鼠被药理学地去势，使用促性腺激素释放激素激动剂Decapeptyl(曲普瑞林-D-Trp(6)-LHRH)慢性给药。其中一半的大鼠接受了17β-雌二醇作为激素替代，而对照组每天只注射赋形剂。我们发现，服用十肽后，卵巢和肾上腺的PBR结合能力分别下降了40%和48%，而肾脏则没有变化。这种PBR密度的下调可被雌二醇替代所阻止。我们没有发现在这种由十肽诱导的下调中存在转录、转录后和翻译机制的证据。相反，用针对PBR复合体18和32 kDa亚基的抗体对PBR复合体的免疫沉淀表明，PBR亚单位的相互作用发生了变化，与PBR结合能力的下调一致。这些发现代表了一种新的激素依赖的翻译后调节机制。
The peripheral benzodiazepine receptor (PBR) is composed of three subunits with molecular masses of 18, 30, and 32 kDa. Many physiological functions have been attributed to the PBR, including regulation of steroidogenesis. Furthermore, the PBR itself is under hormonal regulation. In the current study, we investigated the role of female gonadal sex hormones in the regulation of PBR expression in steroidogenic and nonsteroidogenic tissues. To accomplish this, adult female rats were pharmacologically castrated using chronic administration of the gonadotropin-releasing hormone agonist decapeptyl (triptorelin-D-Trp(6)-LHRH). Half of these rats received 17beta-estradiol as hormone replacement, while a control group received daily injections of vehicle only. We found that PBR binding capacity dropped by 40 and 48% in ovaries and adrenals, respectively, following decapeptyl administration, as opposed to no change in the kidney. This down-regulation of PBR densities was prevented by estradiol replacement. We did not find evidence for transcriptional, posttranscriptional, and translational mechanisms in this decapeptyl-induced down-regulation. In contrast, immunoprecipitation of the PBR complex, using antibodies against the 18- and 32-kDa subunits of the complex, demonstrated that there were changes in PBR subunit interactions, consistent with the down-regulation of PBR binding capacity. These findings represent a novel hormone-dependent posttranslational regulatory mechanism.