Szende B, Srkalovic G, Timar J, Mulchahey J J, Neill J D, Lapis K, Csikos A, Szepeshazi K, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146.
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4153-6. doi: 10.1073/pnas.88.10.4153.
Previous work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormone-releasing hormone (LHRH). Although the regression of experimental pancreatic cancers induced by treatment with LHRH agonists or antagonists could be explained in part by the creation of sex-steroid deficiency, direct effects mediated by LHRH receptors might also play a role. Here, we demonstrate that pancreatic tumor cells do exhibit high-affinity binding sites for LHRH, but only in their nuclei; low-affinity sites are associated with the cell membranes. These binding sites appear to be LHRH receptors since electron microscopic immunohistochemical studies show that an antibody to the LHRH receptor reacted with sites in the nucleus of pancreatic tumor cells. Immunoreactive sites in the nucleus also were found in a restricted set of normal hamster pituitary cells thought to be luteinizing hormone-secreting cells and in MXT mouse mammary tumor cells. Such nuclear receptors may be involved in the transmission of the direct action of LHRH analogues on the tumor cells, resulting in the enhancement of programmed cell death.
先前的研究表明，仓鼠和人类的胰腺肿瘤而非正常胰腺，表现出对促黄体生成素释放激素（LHRH）的低亲和力细胞膜受体。虽然用LHRH激动剂或拮抗剂治疗诱导的实验性胰腺癌的消退，部分可通过性甾体缺乏来解释，但LHRH受体介导的直接作用也可能起作用。在这里，我们证明胰腺肿瘤细胞确实表现出对LHRH的高亲和力结合位点，但仅存在于细胞核中；低亲和力位点与细胞膜相关。这些结合位点似乎是LHRH受体，因为电子显微镜免疫组织化学研究表明，LHRH受体抗体与胰腺肿瘤细胞核中的位点发生反应。在一组被认为是促黄体生成素分泌细胞的正常仓鼠垂体细胞以及MXT小鼠乳腺肿瘤细胞中，也发现了细胞核中的免疫反应位点。这种核受体可能参与LHRH类似物对肿瘤细胞直接作用的传递，从而导致程序性细胞死亡的增强。
