GnRH analogs stimulate phospholipase C activity in mammary tumor membranes: modulation by GTP.
An in vitro assay for phospholipase C activity was developed, employing exogenously added 32P-labelled phosphatidylinositol 4,5-bisphosphate as substrate. This enzymatic assay used to analyse the direct effect of GnRH on mammary tumors. GnRH agonists stimulate membranal phosphoinositide-specific phospholipase C activity. The increase in inositoltrisphosphate production is dose dependent, and is inhibited by the GnRH antagonist Org-30276. We took advantage of this non-cellular assay system for evaluating the role of G-binding proteins in the phosphoinositide transducing system in mammary tumors. GTP gamma S stimulates the basal and GnRH-dependent phospholipase C activity. This effect was abolished by GDP beta S. The cytosolic phospholipase C activity was also stimulated by GTP gamma S but was not affected by the hormone. These results suggest that GnRH may affect the growth of mammary tumors directly and not only through the reduction of blood gonadotropin level.
Segal
T
T
Endocrinology Laboratory, Soroka University Hospital, Beer Sheva, Israel.
Levy
J
J
Sharoni
Y
Y
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000502:physiology*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D010716:Phosphatidylinositols; D010906:Pituitary Hormone-Releasing Hormones; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases