Emanuele N V, Jurgens J, La Paglia N, Williams D W, Kelley M R
Department of Medicine and the Molecular Biology Program, Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois 60153, USA.
J Endocrinol. 1996 Mar;148(3):509-15. doi: 10.1677/joe.0.1480509.
Many studies have consistently shown that castration induces a prompt increase in serum levels and pituitary content of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as a concomitant rise in steady state levels of the messenger RNAs directing their synthesis. The reports of effects of castration on the overall physiology of hypothalamic luteinizing hormone-releasing hormone (LHRH)--steady state levels of LHRH mRNA, post-translational processing and secretion--have, however, not been consistent. The goal of the studies reported here was to provide the first analysis of the effect of castration, at multiple postoperative time points, on steady state levels of LHRH mRNA and on the levels of hypothalamic proLHRH. All these data are correlated with hypothalamic levels of the mature LHRH decapeptide and with serum and pituitary levels of immunoreactive LH and FSH. Adult male rats were either castrated or sham-castrated (controls) and then sacrificed at 1, 3, 5, 7, 14, 21 or 28 days postoperatively. As expected, there was a prompt and sustained rise in serum immunoreactive LH and FSH in castrates compared with sham-operated animals. Intra-pituitary LH levels rose above levels in the sham-operated animals by 14 days post castration. Intra-pituitary FSH showed a biphasic response, first falling significantly below control levels, then rising above control levels at 21 days. Steady state levels of LHRH mRNA in castrates, measured by reverse transcription/polymerase chain reaction, were increased about 2-fold above control levels by 1 day postoperatively, but were virtually identical to control levels at each of the other time points despite marked changes in the gonadotropins. ProLHRH content in castrates was 1.8-times that seen in controls at 1 day post castration (P<0.05), concomitant with the rise in steady state levels of LHRH mRNA at that time point. However, proLHRH content in castrates was no different from that seen in controls at each of the later time points examined. LHRH content was unchanged through 7 days after castration, but then fell significantly to 57% of control levels in hypothalami from animals gonadectomized 14 to 21 days previously (P<0.001 vs control), and to 54% of sham-operated levels at 28 days postoperatively (P<0.001). We conclude that: (1) changes in steady state levels of LHRH mRNA after castration are small and transient and (2) increased proLHRH coupled with unchanged LHRH levels at 1 day post castration, and castrate animal proLHRH at control levels coupled with falling LHRH at later post-castration time points indicate that the effect of gonadectomy on post-translational processing of proLHRH to LHRH is, likewise, small and transient. In aggregate our data suggest that most of the increase in serum LH and FSH seen in male rats after castration is not mediated at the hypothalamic level.
许多研究一致表明，去势会导致血清中促性腺激素、促黄体生成素（LH）和促卵泡激素（FSH）的水平以及垂体含量迅速升高，同时指导其合成的信使RNA的稳态水平也会随之上升。然而，关于去势对下丘脑促黄体生成素释放激素（LHRH）整体生理学的影响——LHRH mRNA的稳态水平、翻译后加工及分泌——的报道并不一致。本文报道的研究目的是首次分析去势在多个术后时间点对LHRH mRNA稳态水平以及下丘脑前体LHRH水平的影响。所有这些数据都与下丘脑成熟LHRH十肽的水平以及血清和垂体中免疫反应性LH和FSH的水平相关。成年雄性大鼠要么接受去势手术，要么进行假手术（作为对照），然后在术后1、3、5、7、14、21或28天处死。正如预期的那样，与假手术动物相比，去势动物血清中免疫反应性LH和FSH迅速且持续升高。去势后14天，垂体LH水平高于假手术动物。垂体FSH呈现双相反应，首先显著低于对照水平，然后在21天时高于对照水平。通过逆转录/聚合酶链反应测量，去势动物术后1天LHRH mRNA的稳态水平比对照水平升高约2倍，但在其他时间点，尽管促性腺激素有明显变化，其水平实际上与对照水平相同。去势后1天，去势动物的前体LHRH含量是对照动物的1.8倍（P<0.05），这与该时间点LHRH mRNA稳态水平的升高一致。然而，在随后检查的各个时间点，去势动物的前体LHRH含量与对照动物并无差异。去势后7天内LHRH含量不变，但在14至21天前接受性腺切除的动物的下丘脑LHRH含量随后显著下降至对照水平的57%（与对照相比，P<0.001），术后28天时降至假手术水平的54%（P<0.001）。我们得出以下结论：（1）去势后LHRH mRNA稳态水平的变化较小且短暂；（2）去势后1天前体LHRH增加而LHRH水平不变，以及去势后后期去势动物前体LHRH处于对照水平而LHRH下降，这表明性腺切除对前体LHRH加工成LHRH的翻译后过程的影响同样较小且短暂。总体而言，我们的数据表明，雄性大鼠去势后血清LH和FSH的大部分升高并非由下丘脑水平介导。
