Batticane N, Morale M C, Gallo F, Farinella Z, Marchetti B
Department of Pharmacology, University of Catania Medical School, Italy.
Endocrinology. 1991 Jul;129(1):277-86. doi: 10.1210/endo-129-1-277.
The marked modulation of lymphocyte function exerted by the hypothalamic decapetide LHRH prompted us to study the possible involvement of the neuropeptide in one of the major steps of lymphocyte proliferation, namely the expression of interleukin-2 (IL-2) receptor during in vitro treatment of rat lymphocytes with LHRH agonists (LHRH-A) or antagonists (LHRH-ANTA). The basal proliferative activity of splenocytes and thymocytes from proestrous female rats was significantly stimulated after incubation with LHRH and LHRH-A, but not LHRH fragments [LHRH-(1-3), LHRH-(1-5), and LHRH-(2-6)]. Similarly, in the absence of the mitogenic stimulus, IL-2 receptor expression was significantly stimulated in thymocyte and splenocyte cultures incubated with increasing doses of LHRH or its agonists. The amplification of Concanavalin-A-induced increase in blastogenic transformation of lymphocytes by LHRH was paralleled by a significant stimulation of IL-2 receptor expression. The specificity of such effect was demonstrated by 1) the failure of LHRH fragments [LHRH-(1-6)] to mimick the LHRH stimulatory effect; and 2) the complete reversal produced by simultaneous addition of a potent LHRH-ANTA on IL-2 receptor expression induced by LHRH. Moreover, basal and lectin stimulation of IL-2 receptor-positive cells were significantly inhibited by treatment with the LHRH-ANTA. These data clearly demonstrate that 1) LHRH induction of lymphocyte activation in vitro is accompanied by a specific increase in IL-2 receptor-positive cells; 2) endogenous lymphocyte LHRH may participate in stimulation of IL-2 receptor expression under both basal and stimulated conditions, suggesting that LHRH signaling at the lymphocyte may interact synergistically with intracellular mechanisms responsible for lymphocyte activation.
下丘脑十肽促性腺激素释放激素（LHRH）对淋巴细胞功能的显著调节作用促使我们研究该神经肽在淋巴细胞增殖的一个主要步骤中可能发挥的作用，即在体外使用LHRH激动剂（LHRH-A）或拮抗剂（LHRH-ANTA）处理大鼠淋巴细胞时白细胞介素-2（IL-2）受体的表达。与LHRH和LHRH-A孵育后，动情前期雌性大鼠脾细胞和胸腺细胞的基础增殖活性受到显著刺激，但LHRH片段[LHRH-(1-3)、LHRH-(1-5)和LHRH-(2-6)]则无此作用。同样，在没有促有丝分裂刺激的情况下，用递增剂量的LHRH或其激动剂孵育的胸腺细胞和脾细胞培养物中，IL-2受体表达受到显著刺激。LHRH对伴刀豆球蛋白A诱导的淋巴细胞增殖转化增加的放大作用与IL-2受体表达的显著刺激平行。这种作用的特异性通过以下两点得以证明：1）LHRH片段[LHRH-(1-6)]无法模拟LHRH的刺激作用；2）同时添加强效LHRH-ANTA可完全逆转LHRH诱导的IL-2受体表达。此外，LHRH-ANTA处理可显著抑制IL-2受体阳性细胞的基础刺激和凝集素刺激。这些数据清楚地表明：1）体外LHRH诱导淋巴细胞活化伴随着IL-2受体阳性细胞的特异性增加；2）内源性淋巴细胞LHRH可能在基础和刺激条件下均参与刺激IL-2受体表达，这表明淋巴细胞处的LHRH信号可能与负责淋巴细胞活化的细胞内机制协同相互作用。
