title: Receptors for D-Trp6-luteinizing hormone-releasing hormone, somatostatin, and insulin-like growth factor I in MXT mouse mammary carcinoma.
abstract: Membrane receptors for D-Trp6-luteinizing hormone-releasing hormone (D-Trp6-LH-RH), somatostatin-14 (SS-14), and insulin-like growth factor I (IGF-I) were estimated in MXT mammary cancers of mice using sensitive multipoint micromethods. The receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist D-Trp6-LH-RH and the somatostatin analog RC-160, which strongly inhibited tumor growth. In the control group, D-Trp6-LH-RH was bound to the single class of saturable, specific, noncooperative receptor sites (Kd, = 29.3 +/- 8.48 x 10(-9) M; Bmax = 4.55 +/- 0.31 pmol/mg membrane protein). Treatment with D-Trp6-LH-RH alone or in combination with RC-160 produced down-regulation of membrane receptors for D-Trp6-LH-RH on MXT mammary tumor cells. RC-160 alone and ovariectomy were without effect on D-Trp6-LH-RH receptors. On the membrane surface of MXT mammary cells, we found one class of high affinity, specific, saturable binding sites for SS-14 (Kd = 4.4 +/- 1.9 x 10(-9) M; Bmax = 0.58 +/- 0.21 pmol/mg membrane protein). Treatment with RC-160 alone or combined with D-Trp6-LH-RH significantly increased both the dissociation binding constant (Kd = 18.6 +/- 3.5 x 10(-9) and 10.1 +/- 0.7 x 10(-9) M, respectively) and the binding capacity (Bmax = 13.98 +/- 1.7 and 21.00 +/- 4.0 pmol/mg membrane protein, respectively). We also found specific binding sites (Kd = 3.01 +/- 0.15 x 10(-9) M; Bmax = 2.24 +/- 0.96 pmol/mg membrane protein) for IGF-I in the membrane fractions of MXT mammary cancers. Chronic treatment with D-Trp6-LH-RH and RC-160 alone or in combination, as well as ovariectomy, significantly decreased the dissociation binding constant of IGF-I membrane receptors on MXT mammary cells. Our results strongly suggest an important role of LH-RH, SS-14, and IGF-I in the growth of MXT mammary carcinoma. Changes in characteristics of receptors after treatment with analogs of LH-RH and SS-14 along with tumor growth inhibition provide additional support for the direct effect of these peptides on tumor cells. A possible significance of these findings as applied to a clinical environment is discussed.
authors.affiliation: Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana.
authors.forename: G
authors.initials: G
authors.lastname: Srkalovic
authors.forename: B
authors.initials: B
authors.lastname: Szende
authors.forename: T W
authors.initials: TW
authors.lastname: Redding
authors.forename: K
authors.initials: K
authors.lastname: Groot
authors.forename: A V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D002462:Cell Membrane / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000032:analysis* / Q000188:drug therapy; D051379:Mice; D010052:Ovariectomy; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D011966:Receptors, LHRH / Q000032:analysis* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000378:metabolism; D017451:Receptors, Somatomedin; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017329:Triptorelin Pamoate
chemical_list: D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D017981:Receptors, Neurotransmitter; D017451:Receptors, Somatomedin; D017481:Receptors, Somatostatin; D017329:Triptorelin Pamoate; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I