Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.
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.
Szende
B
B
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146.
Srkalovic
G
G
Timar
J
J
Mulchahey
J J
JJ
Neill
J D
JD
Lapis
K
K
Csikos
A
A
Szepeshazi
K
K
Schally
A V
AV
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D006224:Cricetinae; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry*; D008647:Mesocricetus; D051379:Mice; D008854:Microscopy, Electron; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D011966:Receptors, LHRH / Q000032:analysis* / Q000378:metabolism
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone